{"entity": "researcher", "timestamp": "2026-08-20T20:54:03.586Z", "family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "affiliations": ["Danish Cancer Society Research Center, Copenhagen, Denmark. apomm@cancer.dk."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543"}}, "publications": [{"entity": "publication", "iuid": "5137acade2f14370b914614b3b1b44fa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5137acade2f14370b914614b3b1b44fa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5137acade2f14370b914614b3b1b44fa"}}, "title": "The PP2A-B55\u03b1 phosphatase is a master regulator of mitochondrial degradation and biogenesis.", "authors": [{"family": "Cianfanelli", "given": "Valentina", "initials": "V", "orcid": "0000-0002-3857-9463", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecd317d35f4142febdd006e4c19ecd3b.json"}}, {"family": "Nanni", "given": "Monica", "initials": "M", "orcid": "0000-0001-5706-0053", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/09b0dc7e755640268eb404b8984fe701.json"}}, {"family": "Corr\u00e0", "given": "Samantha", "initials": "S", "orcid": "0000-0003-1985-6194", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34aed5b4b7d14834bcbcd1550714f9ef.json"}}, {"family": "Mauri", "given": "Sofia", "initials": "S", "orcid": "0000-0003-3931-1490", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0e0ea3075fda4ba18327bc96a9123f69.json"}}, {"family": "Sumpton", "given": "David", "initials": "D", "orcid": "0000-0002-9004-4079", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f3a17d1b74741f8bccfff7c0ad05b19.json"}}, {"family": "Lilla", "given": "Sergio", "initials": "S", "orcid": "0000-0003-3142-7640", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7a5956d3819947df8122ec1601025bbc.json"}}, {"family": "De Cegli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-8526-8692", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1269d7def39540659533698e1282ce13.json"}}, {"family": "Bordi", "given": "Matteo", "initials": "M", "orcid": "0000-0001-8207-8546", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c34176b2b1141f6a41d23f49de8e4ec.json"}}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Ferraina", "given": "Caterina", "initials": "C", "orcid": "0000-0002-3770-4437", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb9f5ebe210040f78d03e3bc8503c727.json"}}, {"family": "Hall", "given": "Arnaldur", "initials": "A", "orcid": "0000-0001-6847-4438", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f4c8a78056504735b11d15abd86dc46d.json"}}, {"family": "Petraroia", "given": "Michele", "initials": "M", "orcid": "0009-0000-0329-1155", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/10cc6330b16e4a338e87c3a38ccb36da.json"}}, {"family": "Clausi", "given": "Valentina", "initials": "V", "orcid": "0009-0008-2662-4774", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ce4a5d2f745b392ee0a6e92f65b5d.json"}}, {"family": "Giorda", "given": "Ezio", "initials": "E", "orcid": "0000-0002-5875-832X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6005bedf7cd44c678a5e50a999ba06dd.json"}}, {"family": "Scarsella", "given": "Marco", "initials": "M", "orcid": "0000-0002-3386-9664", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c8fe29ee7e764f6bb29092e11f52c6f9.json"}}, {"family": "Barbiera", "given": "Alessandra", "initials": "A", "orcid": "0000-0002-2051-2359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c18e2aab6af747439958edfa9be888a7.json"}}, {"family": "Cadeddu", "given": "Giulia", "initials": "G", "orcid": "0000-0003-1841-8395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c209292faee4904bda06ce017551fd8.json"}}, {"family": "Colasanti", "given": "Marco", "initials": "M", "orcid": "0000-0002-5752-4943", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/479c78cbd64a455a9b7f5cbedd475fa0.json"}}, {"family": "Persichini", "given": "Tiziana", "initials": "T", "orcid": "0000-0001-8291-6706", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d80e8c50c4f45b8b13eda46cbbc3067.json"}}, {"family": "Maeda", "given": "Kenji", "initials": "K", "orcid": "0000-0002-9080-5691", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9dc9c0792c6c44e29090a2683a73f884.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Di Malta", "given": "Chiara", "initials": "C", "orcid": "0000-0001-6524-4354", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bef2e1eff2cf49f6ba6da220d8e76d2c.json"}}, {"family": "Locatelli", "given": "Franco", "initials": "F", "orcid": "0000-0002-7976-3654", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2687cc638c754f099e9a76deec1d8911.json"}}, {"family": "Zanivan", "given": "Sara", "initials": "S"}, {"family": "Ismail", "given": "Shehab", "initials": "S", "orcid": "0000-0002-4150-1077", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1587edc23d6043eb8c3be75259ef47e2.json"}}, {"family": "Ziviani", "given": "Elena", "initials": "E"}, {"family": "Cecconi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-5614-4359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1736eeb3ba3d4b0f80058b507487c5e1.json"}}], "type": "journal article", "published": "2025-10-03", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "40", "pages": "eadw7376", "issn-l": "2375-2548"}, "abstract": "Mitochondrial homeostasis relies on a tight balance between mitochondrial biogenesis and degradation. Although mitophagy is one of the main pathways involved in the clearance of damaged or old mitochondria, its coordination with mitochondrial biogenesis is poorly characterized. Here, by unbiased approaches including last-generation liquid chromatography coupled to mass spectrometry and transcriptomics, we identify the protein phosphatase PP2A-B55\u03b1/PPP2R2A as a Parkin-dependent regulator of mitochondrial number. Upon mitochondrial damage, PP2A-B55\u03b1 determines the amplitude of mitophagy induction and execution by regulating both early and late mitophagy events. A few minutes after the insult, ULK1 is released from the inhibitory regulation of PP2A-B55\u03b1, whereas 2 to 4 hours later, PP2A-B55\u03b1 promotes the nuclear translocation of TFEB, the master regulator of autophagy and lysosome genes, to support mitophagy execution. Moreover, PP2A-B55\u03b1 controls a transcriptional program of mitochondrial biogenesis by stabilizing the Parkin substrate and PGC-1\u03b1 inhibitor PARIS. PP2A-B55\u03b1 targeting rescues neurodegenerative phenotypes in a fly model of Parkinson's disease, thus suggesting potential therapeutic application.", "doi": "10.1126/sciadv.adw7376", "pmid": "41042873", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12494018"}], "notes": [], "created": "2026-08-20T11:59:09.713Z", "modified": "2026-08-20T11:59:10.839Z"}, {"entity": "publication", "iuid": "6703dfab66c94278856a80aba8102dc7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6703dfab66c94278856a80aba8102dc7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6703dfab66c94278856a80aba8102dc7"}}, "title": "NAD+ regulates nucleotide metabolism and genomic DNA replication.", "authors": [{"family": "Munk", "given": "Sebastian Howen Nesgaard", "initials": "SHN", "orcid": "0000-0002-4601-4833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c30767aaac5401696179217992498a0.json"}}, {"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Adelantado Rubio", "given": "Alba", "initials": "A"}, {"family": "Hall", "given": "Arnaldur", "initials": "A"}, {"family": "Pappas", "given": "George", "initials": "G"}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Lee", "given": "MyungHee", "initials": "M"}, {"family": "Johnsen", "given": "Lea Gi\u00f8rtz", "initials": "LG", "orcid": "0000-0002-0744-0899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ddbbcb25f0b54c0288252fc69b1d53d9.json"}}, {"family": "Guldberg", "given": "Per", "initials": "P"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Nat. Cell Biol.", "issn": "1476-4679", "volume": "25", "issue": "12", "pages": "1774-1786", "issn-l": "1465-7392"}, "abstract": "The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb's cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb's cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.", "doi": "10.1038/s41556-023-01280-z", "pmid": "37957325", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10709141"}, {"db": "pii", "key": "10.1038/s41556-023-01280-z"}], "notes": [], "created": "2026-08-20T08:55:00.963Z", "modified": "2026-08-20T08:55:01.154Z"}, {"entity": "publication", "iuid": "3350a4ecba3048d8a01a1780046ae17a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/3350a4ecba3048d8a01a1780046ae17a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/3350a4ecba3048d8a01a1780046ae17a"}}, "title": "Human cytomegalovirus hijacks host stress response fueling replication stress and genome instability.", "authors": [{"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Galanos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0003-1403-4685", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d1071fd28cb42d6b328182cddfd341f.json"}}, {"family": "Pantalone", "given": "Mattia Russel", "initials": "MR", "orcid": "0000-0002-2706-4683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec002c989634427fb962892d402972c9.json"}}, {"family": "Lee", "given": "MyungHee", "initials": "M"}, {"family": "Cui", "given": "Huanhuan L", "initials": "HL"}, {"family": "Shilling", "given": "Patrick J", "initials": "PJ"}, {"family": "Br\u00f8chner", "given": "Christian Beltoft", "initials": "CB"}, {"family": "Broholm", "given": "Helle", "initials": "H"}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "S\u00f6derberg-Naucler", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-8955-3610", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ef2ba2f309064cddae2548ffa1b84145.json"}}], "type": "journal article", "published": "2022-08-00", "journal": {"title": "Cell Death Differ.", "issn": "1476-5403", "volume": "29", "issue": "8", "pages": "1639-1653", "issn-l": "1350-9047"}, "abstract": "Viral infections enhance cancer risk and threaten host genome integrity. Although human cytomegalovirus (HCMV) proteins have been detected in a wide spectrum of human malignancies and HCMV infections have been implicated in tumorigenesis, the underlying mechanisms remain poorly understood. Here, we employed a range of experimental approaches, including single-molecule DNA fiber analysis, and showed that infection by any of the four commonly used HCMV strains: AD169, Towne, TB40E or VR1814 induced replication stress (RS), as documented by host-cell replication fork asymmetry and formation of 53BP1 foci. The HCMV-evoked RS triggered an ensuing host DNA damage response (DDR) and chromosomal instability in both permissive and non-permissive human cells, the latter being particularly relevant in the context of tumorigenesis, as such cells can survive and proliferate after HCMV infection. The viral major immediate early enhancer and promoter (MIEP) that controls expression of the viral genes IE72 (IE-1) and IE86 (IE-2), contains transcription-factor binding sites shared by promoters of cellular stress-response genes. We found that DNA damaging insults, including those relevant for cancer therapy, enhanced IE72/86 expression. Thus, MIEP has been evolutionary shaped to exploit host DDR. Ectopically expressed IE72 and IE86 also induced RS and increased genomic instability. Of clinical relevance, we show that undergoing standard-of-care genotoxic radio-chemotherapy in patients with HCMV-positive glioblastomas correlated with elevated HCMV protein markers after tumor recurrence. Collectively, these results are consistent with our proposed concept of HCMV hijacking transcription-factor binding sites shared with host stress-response genes. We present a model to explain the potential oncomodulatory effects of HCMV infections through enhanced replication stress, subverted DNA damage response and induced genomic instability.", "doi": "10.1038/s41418-022-00953-w", "pmid": "35194187", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9346009"}, {"db": "pii", "key": "10.1038/s41418-022-00953-w"}, {"db": "ClinicalTrials.gov", "key": "NCT04116411"}], "notes": [], "created": "2026-08-20T08:49:23.671Z", "modified": "2026-08-20T08:49:23.870Z"}, {"entity": "publication", "iuid": "6682d4bfc0a5422cbb4226b0c7785168", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6682d4bfc0a5422cbb4226b0c7785168.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6682d4bfc0a5422cbb4226b0c7785168"}}, "title": "p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.", "authors": [{"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/069306b8ab85484db417a144c0a7d325.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "Cell Death Differ.", "issn": "1476-5403", "volume": "29", "issue": "5", "pages": "972-982", "issn-l": "1350-9047"}, "abstract": "Despite several decades of intense research focused on understanding function(s) and disease-associated malfunction of p53, there is no sign of any \"mid-life crisis\" in this rapidly advancing area of biomedicine. Firmly established as the hub of cellular stress responses and tumor suppressor targeted in most malignancies, p53's many talents continue to surprise us, providing not only fresh insights into cell and organismal biology, but also new avenues to cancer treatment. Among the most fruitful lines of p53 research in recent years have been the discoveries revealing the multifaceted roles of p53-centered pathways in the fundamental processes of DNA replication and ribosome biogenesis (RiBi), along with cellular responses to replication and RiBi stresses, two intertwined areas of cell (patho)physiology that we discuss in this review. Here, we first provide concise introductory notes on the canonical roles of p53, the key interacting proteins, downstream targets and post-translational modifications involved in p53 regulation. We then highlight the emerging involvement of p53 as a key component of the DNA replication Fork Speed Regulatory Network and the mechanistic links of p53 with cellular checkpoint responses to replication stress (RS), the driving force of cancer-associated genomic instability. Next, the tantalizing, yet still rather foggy functional crosstalk between replication and RiBi (nucleolar) stresses is considered, followed by the more defined involvement of p53-mediated monitoring of the multistep process of RiBi, including the latest updates on the RPL5/RPL11/5 S rRNA-MDM2-p53-mediated Impaired Ribosome Biogenesis Checkpoint (IRBC) pathway and its involvement in tumorigenesis. The diverse defects of RiBi and IRBC that predispose and/or contribute to severe human pathologies including developmental syndromes and cancer are then outlined, along with examples of promising small-molecule-based strategies to therapeutically target the RS- and particularly RiBi- stress-tolerance mechanisms to which cancer cells are addicted due to their aberrant DNA replication, repair, and proteo-synthesis demands.", "doi": "10.1038/s41418-022-00999-w", "pmid": "35444234", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9090812"}, {"db": "pii", "key": "10.1038/s41418-022-00999-w"}], "notes": [], "created": "2026-08-20T08:49:26.066Z", "modified": "2026-08-20T08:49:26.145Z"}, {"entity": "publication", "iuid": "12a923d86f454f0da28ae57d3a170b0d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/12a923d86f454f0da28ae57d3a170b0d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/12a923d86f454f0da28ae57d3a170b0d"}}, "title": "Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution.", "authors": [{"family": "Venkatesan", "given": "Subramanian", "initials": "S", "orcid": "0000-0001-6454-8508", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecacc5d56e504429823daac1d5ea2aeb.json"}}, {"family": "Angelova", "given": "Mihaela", "initials": "M", "orcid": "0000-0002-0495-9695", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2d1d07f07b24def81b4d5ee64b6c60a.json"}}, {"family": "Puttick", "given": "Clare", "initials": "C"}, {"family": "Zhai", "given": "Haoran", "initials": "H"}, {"family": "Caswell", "given": "Deborah R", "initials": "DR", "orcid": "0000-0002-7550-5092", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225c5bd5807a44398be2cce8dcc25b52.json"}}, {"family": "Lu", "given": "Wei-Ting", "initials": "WT", "orcid": "0000-0002-1405-4806", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8acbe8b1a0394c668ccf21845b0b673e.json"}}, {"family": "Dietzen", "given": "Michelle", "initials": "M", "orcid": "0000-0002-6853-7563", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4408177a45c844b58fb9ea4f7538d9b9.json"}}, {"family": "Galanos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0003-1403-4685", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d1071fd28cb42d6b328182cddfd341f.json"}}, {"family": "Evangelou", "given": "Konstantinos", "initials": "K"}, {"family": "Bellelli", "given": "Roberto", "initials": "R"}, {"family": "Lim", "given": "Emilia L", "initials": "EL"}, {"family": "Watkins", "given": "Thomas B K", "initials": "TBK"}, {"family": "Rowan", "given": "Andrew", "initials": "A"}, {"family": "Teixeira", "given": "Vitor H", "initials": "VH"}, {"family": "Zhao", "given": "Yue", "initials": "Y"}, {"family": "Chen", "given": "Haiquan", "initials": "H", "orcid": "0000-0003-1689-0549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdc6fa9477f94f12a85b5034d7728fff.json"}}, {"family": "Ngo", "given": "Bryan", "initials": "B"}, {"family": "Zalmas", "given": "Lykourgos-Panagiotis", "initials": "LP", "orcid": "0000-0002-4317-7709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e669bc02b2544f9cb61ac71d69f91a81.json"}}, {"family": "Al Bakir", "given": "Maise", "initials": "M"}, {"family": "Hobor", "given": "Sebastijan", "initials": "S"}, {"family": "Gr\u00f6nroos", "given": "Eva", "initials": "E", "orcid": "0000-0001-8303-5409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1fa0868fdf094f1da9bd53d4ea2b0b5d.json"}}, {"family": "Pennycuick", "given": "Adam", "initials": "A", "orcid": "0000-0001-5836-0250", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f4eb0288b96e4807b1b119c754b7aca1.json"}}, {"family": "Nigro", "given": "Ersilia", "initials": "E"}, {"family": "Campbell", "given": "Brittany B", "initials": "BB"}, {"family": "Brown", "given": "William L", "initials": "WL", "orcid": "0000-0001-5354-9468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/624b4fe15f824b74879cf42fa268e513.json"}}, {"family": "Akarca", "given": "Ayse U", "initials": "AU", "orcid": "0000-0003-0629-3927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bef78ecdb9fc4468bc0ffdbf923662e0.json"}}, {"family": "Marafioti", "given": "Teresa", "initials": "T", "orcid": "0000-0003-1223-6275", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b9e1588b9284cdeb7e70851280c0d6b.json"}}, {"family": "Wu", "given": "Mary Y", "initials": "MY", "orcid": "0000-0002-2074-6171", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3230e045491e4089b405c8eddba57e12.json"}}, {"family": "Howell", "given": "Michael", "initials": "M", "orcid": "0000-0003-0912-0079", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/111f5b9b742640e5b51e15b8b0873a95.json"}}, {"family": "Boulton", "given": "Simon J", "initials": "SJ", "orcid": "0000-0002-1125-8977", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54b9e78ef54347b39a8dd5ec4323837d.json"}}, {"family": "Bertoli", "given": "Cosetta", "initials": "C"}, {"family": "Fenton", "given": "Tim R", "initials": "TR", "orcid": "0000-0002-4737-8233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ea5c50a61a3747b99fd706c00ab6bafe.json"}}, {"family": "de Bruin", "given": "Robertus A M", "initials": "RAM", "orcid": "0000-0001-9957-1409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50a1997f1625452b862d9ecaf48f3036.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Santoni-Rugiu", "given": "Eric", "initials": "E", "orcid": "0000-0002-2283-3535", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36e80a5162c54a45a4b4e26b4508175d.json"}}, {"family": "Hynds", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-2170-8791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d363c63598224cb0bd24dffc46d0d3eb.json"}}, {"family": "Gorgoulis", "given": "Vassilis G", "initials": "VG", "orcid": "0000-0001-9001-4112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4f7462e5c510438485b3fa91671db801.json"}}, {"family": "Jamal-Hanjani", "given": "Mariam", "initials": "M"}, {"family": "McGranahan", "given": "Nicholas", "initials": "N"}, {"family": "Harris", "given": "Reuben S", "initials": "RS"}, {"family": "Janes", "given": "Sam M", "initials": "SM", "orcid": "0000-0002-6634-5939", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/310b5ae62b03414d8cc9169b827057c6.json"}}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Bakhoum", "given": "Samuel F", "initials": "SF"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Kanu", "given": "Nnennaya", "initials": "N"}, {"family": "Swanton", "given": "Charles", "initials": "C", "orcid": "0000-0002-4299-3018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e624db9004da4812a607b34b20cea0e7.json"}}, {"family": "TRACERx Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2021-10-00", "journal": {"title": "Cancer Discov", "issn": "2159-8290", "volume": "11", "issue": "10", "pages": "2456-2473", "issn-l": "2159-8274"}, "abstract": "APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non-small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. SIGNIFICANCE: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution.This article is highlighted in the In This Issue feature, p. 2355.", "doi": "10.1158/2159-8290.CD-20-0725", "pmid": "33947663", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1710791"}, {"db": "pmc", "key": "PMC8487921"}, {"db": "pii", "key": "2159-8290.CD-20-0725"}], "notes": [], "created": "2026-08-20T12:14:28.881Z", "modified": "2026-08-20T12:14:29.593Z"}, {"entity": "publication", "iuid": "5ea43ffa349f444181e1acfaacf914ed", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5ea43ffa349f444181e1acfaacf914ed.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5ea43ffa349f444181e1acfaacf914ed"}}, "title": "The human nucleoporin Tpr protects cells from RNA-mediated replication stress.", "authors": [{"family": "Kosar", "given": "Martin", "initials": "M", "orcid": "0000-0002-9400-2327", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21ca71e4ec374b618abe9722627ecf2d.json"}}, {"family": "Giannattasio", "given": "Michele", "initials": "M", "orcid": "0000-0001-7099-5718", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d1b94f91381249bb83cc9742c7edd4b4.json"}}, {"family": "Piccini", "given": "Daniele", "initials": "D", "orcid": "0000-0001-9200-8496", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/468948352ff146beb99dc430b9f153b6.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Garc\u00eda-Ben\u00edtez", "given": "Francisco", "initials": "F"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Barroso", "given": "Sonia I", "initials": "SI", "orcid": "0000-0002-0062-2016", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/37a0b52bdbe64a1c884d5e02c49927ff.json"}}, {"family": "Gaillard", "given": "H\u00e9l\u00e8ne", "initials": "H", "orcid": "0000-0002-5740-0641", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/961deb0e44d5438ca505c21a45526ec6.json"}}, {"family": "Martini", "given": "Emanuele", "initials": "E", "orcid": "0000-0002-3375-7726", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04481a4fe5eb4fa28409b51f4333cfae.json"}}, {"family": "Restuccia", "given": "Umberto", "initials": "U"}, {"family": "Ramirez-Otero", "given": "Miguel Angel", "initials": "MA", "orcid": "0000-0001-8428-1150", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/20745976fd6f4c59831c9c78d5069a9b.json"}}, {"family": "Garre", "given": "Massimiliano", "initials": "M"}, {"family": "Verga", "given": "Eleonora", "initials": "E"}, {"family": "And\u00fajar-S\u00e1nchez", "given": "Miguel", "initials": "M", "orcid": "0000-0002-4858-6915", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e4670566116349baaf46842b74fc8c2d.json"}}, {"family": "Maynard", "given": "Scott", "initials": "S", "orcid": "0000-0001-5625-936X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/608188a808184753bc3ed43e2911154c.json"}}, {"family": "Hodny", "given": "Zdenek", "initials": "Z"}, {"family": "Costanzo", "given": "Vincenzo", "initials": "V"}, {"family": "Kumar", "given": "Amit", "initials": "A", "orcid": "0000-0003-1732-440X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8fa80f08c954440a9cadd6dce14a7528.json"}}, {"family": "Bachi", "given": "Angela", "initials": "A", "orcid": "0000-0003-4842-6556", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22f10333c9b3498cb8805d5b9352898f.json"}}, {"family": "Aguilera", "given": "Andr\u00e9s", "initials": "A", "orcid": "0000-0003-4782-1714", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/813e18ed79fb4c53b9a22fb1ac76b3c0.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Foiani", "given": "Marco", "initials": "M", "orcid": "0000-0003-4795-834X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/374821b873e6444c975d79c5a1f309ea.json"}}], "type": "journal article", "published": "2021-06-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "3937", "issn-l": "2041-1723"}, "abstract": "Although human nucleoporin Tpr is frequently deregulated in cancer, its roles are poorly understood. Here we show that Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability. DNA fiber assays and electron microscopy visualization of replication intermediates show that Tpr deficient cells exhibit slow and asymmetric replication forks under replication stress. Tpr deficiency evokes enhanced levels of DNA-RNA hybrids. Additionally, complementary proteomic strategies identify a network of Tpr-interacting proteins mediating RNA processing, such as MATR3 and SUGP2, and functional experiments confirm that their depletion trigger cellular phenotypes shared with Tpr deficiency. Mechanistic studies reveal the interplay of Tpr with GANP, a component of the TREX-2 complex. The Tpr-GANP interaction is supported by their shared protein level alterations in a cohort of ovarian carcinomas. Our results reveal links between nucleoporins, DNA transcription and replication, and the existence of a network physically connecting replication forks with transcription, splicing, and mRNA export machinery.", "doi": "10.1038/s41467-021-24224-3", "pmid": "34168151", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8225803"}, {"db": "pii", "key": "10.1038/s41467-021-24224-3"}], "notes": [], "created": "2026-08-20T08:51:33.116Z", "modified": "2026-08-20T08:51:33.756Z"}, {"entity": "publication", "iuid": "b7277dd6ce53475d840bb9e1376bb4fd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b7277dd6ce53475d840bb9e1376bb4fd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b7277dd6ce53475d840bb9e1376bb4fd"}}, "title": "AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.", "authors": [{"family": "Maiani", "given": "Emiliano", "initials": "E", "orcid": "0000-0003-1432-5394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/28a7ce582c73429f8723c52f53c39136.json"}}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Nazio", "given": "Francesca", "initials": "F"}, {"family": "Holdgaard", "given": "S\u00f8s Gr\u00f8nb\u00e6k", "initials": "SG"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Rizza", "given": "Salvatore", "initials": "S", "orcid": "0000-0001-7335-4684", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6105a9f41af4c54bdf0b74c11a5701f.json"}}, {"family": "Cianfanelli", "given": "Valentina", "initials": "V", "orcid": "0000-0002-3857-9463", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecd317d35f4142febdd006e4c19ecd3b.json"}}, {"family": "Lorente", "given": "Mar", "initials": "M"}, {"family": "Simoneschi", "given": "Daniele", "initials": "D", "orcid": "0000-0003-0448-4295", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ef930f13dc34b09893d417f99a1822c.json"}}, {"family": "Di Marco", "given": "Miriam", "initials": "M"}, {"family": "D'Acunzo", "given": "Pasquale", "initials": "P", "orcid": "0000-0001-7237-0076", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae134a21c0f44416a8f7825d3985d465.json"}}, {"family": "Di Leo", "given": "Luca", "initials": "L", "orcid": "0000-0002-2419-2196", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b38f503dd3d34de885137408e2b10daf.json"}}, {"family": "Rasmussen", "given": "Rikke", "initials": "R"}, {"family": "Montagna", "given": "Costanza", "initials": "C"}, {"family": "Raciti", "given": "Marilena", "initials": "M"}, {"family": "De Stefanis", "given": "Cristiano", "initials": "C"}, {"family": "Gabicagogeascoa", "given": "Estibaliz", "initials": "E"}, {"family": "Rona", "given": "Gergely", "initials": "G"}, {"family": "Salvador", "given": "N\u00e9lida", "initials": "N"}, {"family": "Pupo", "given": "Emanuela", "initials": "E"}, {"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Daniel", "given": "Colin J", "initials": "CJ"}, {"family": "Carinci", "given": "Marianna", "initials": "M"}, {"family": "Cesarini", "given": "Valeriana", "initials": "V"}, {"family": "O'sullivan", "given": "Alfie", "initials": "A"}, {"family": "Jeong", "given": "Yeon-Tae", "initials": "YT"}, {"family": "Bordi", "given": "Matteo", "initials": "M", "orcid": "0000-0001-8207-8546", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c34176b2b1141f6a41d23f49de8e4ec.json"}}, {"family": "Russo", "given": "Francesco", "initials": "F"}, {"family": "Campello", "given": "Silvia", "initials": "S", "orcid": "0000-0003-0536-2484", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2efe505b1c654d21a2e1bc7747b8d739.json"}}, {"family": "Gallo", "given": "Angela", "initials": "A"}, {"family": "Filomeni", "given": "Giuseppe", "initials": "G", "orcid": "0000-0002-2719-1412", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d3fdc6c498f4104a43fa2d2198ef484.json"}}, {"family": "Lanzetti", "given": "Letizia", "initials": "L", "orcid": "0000-0001-7541-5524", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b2da7f657203439d8bc75b048c181dd2.json"}}, {"family": "Sears", "given": "Rosalie C", "initials": "RC", "orcid": "0000-0003-1558-2413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6cc5e16675434a58b04b0db6ad618167.json"}}, {"family": "Hamerlik", "given": "Petra", "initials": "P"}, {"family": "Bartolazzi", "given": "Armando", "initials": "A", "orcid": "0000-0001-7820-5127", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d5a218ebfcd45b4aae83562b6801f33.json"}}, {"family": "Hynds", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-2170-8791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d363c63598224cb0bd24dffc46d0d3eb.json"}}, {"family": "Pearce", "given": "David R", "initials": "DR", "orcid": "0000-0001-8443-2924", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e102ef6912747fba625f94fb0d8b774.json"}}, {"family": "Swanton", "given": "Charles", "initials": "C", "orcid": "0000-0002-4299-3018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e624db9004da4812a607b34b20cea0e7.json"}}, {"family": "Pagano", "given": "Michele", "initials": "M"}, {"family": "Velasco", "given": "Guillermo", "initials": "G", "orcid": "0000-0002-1994-2386", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc733f7578d48739bceff94fbc156cb.json"}}, {"family": "Papaleo", "given": "Elena", "initials": "E"}, {"family": "De Zio", "given": "Daniela", "initials": "D", "orcid": "0000-0002-9454-402X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9493b5e7aab54818b2142490af5ea7b9.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Locatelli", "given": "Franco", "initials": "F"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Cecconi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-5614-4359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1736eeb3ba3d4b0f80058b507487c5e1.json"}}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "592", "issue": "7856", "pages": "799-803", "issn-l": "0028-0836"}, "abstract": "Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway1,2. Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis.", "doi": "10.1038/s41586-021-03422-5", "pmid": "33854232", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1776644"}, {"db": "pmc", "key": "PMC8864551"}, {"db": "pii", "key": "10.1038/s41586-021-03422-5"}], "notes": [], "created": "2026-08-20T08:56:26.998Z", "modified": "2026-08-20T08:57:56.476Z"}, {"entity": "publication", "iuid": "a1a1e07a38b940d48debcc966a6b2574", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a1a1e07a38b940d48debcc966a6b2574.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a1a1e07a38b940d48debcc966a6b2574"}}, "title": "Super-sonic speed of DNA synthesis in medulloblastoma.", "authors": [{"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "volume": "1", "issue": "8", "pages": "758-760", "issn-l": null}, "abstract": null, "doi": "10.1038/s43018-020-0105-8", "pmid": "35122053", "labels": [], "xrefs": [{"db": "pii", "key": "10.1038/s43018-020-0105-8"}], "notes": [], "created": "2026-08-20T09:26:02.998Z", "modified": "2026-08-20T09:26:03.075Z"}, {"entity": "publication", "iuid": "8f2caf91ad654fa19b53bfbbf0da76ca", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8f2caf91ad654fa19b53bfbbf0da76ca.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8f2caf91ad654fa19b53bfbbf0da76ca"}}, "title": "Autophagy role(s) in response to oncogenes and DNA replication stress.", "authors": [{"family": "Vanzo", "given": "Riccardo", "initials": "R"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Hall", "given": "Arnaldur", "initials": "A"}, {"family": "Bouchal", "given": "Jan", "initials": "J"}, {"family": "Dyrskj\u00f8t", "given": "Lars", "initials": "L"}, {"family": "Frankel", "given": "Lisa B", "initials": "LB", "orcid": "0000-0001-7249-3607", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3fe68b077dee407c8a16308fc065026b.json"}}, {"family": "Gorgoulis", "given": "Vassilis", "initials": "V"}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "J\u00e4\u00e4ttel\u00e4", "given": "Marja", "initials": "M", "orcid": "0000-0001-5950-7111", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad3653231c9d4886b5ffefc302030fd1.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Cell Death Differ.", "issn": "1476-5403", "volume": "27", "issue": "3", "pages": "1134-1153", "issn-l": "1350-9047"}, "abstract": "Autophagy is an evolutionarily conserved process that captures aberrant intracellular proteins and/or damaged organelles for delivery to lysosomes, with implications for cellular and organismal homeostasis, aging and diverse pathologies, including cancer. During cancer development, autophagy may play both tumour-supporting and tumour-suppressing roles. Any relationships of autophagy to the established oncogene-induced replication stress (RS) and the ensuing DNA damage response (DDR)-mediated anti-cancer barrier in early tumorigenesis remain to be elucidated. Here, assessing potential links between autophagy, RS and DDR, we found that autophagy is enhanced in both early and advanced stages of human urinary bladder and prostate tumorigenesis. Furthermore, a high-content, single-cell-level microscopy analysis of human cellular models exposed to diverse genotoxic insults showed that autophagy is enhanced in cells that experienced robust DNA damage, independently of the cell-cycle position. Oncogene- and drug-induced RS triggered first DDR and later autophagy. Unexpectedly, genetic inactivation of autophagy resulted in RS, despite cellular retention of functional mitochondria and normal ROS levels. Moreover, recovery from experimentally induced RS required autophagy to support DNA synthesis. Consistently, RS due to the absence of autophagy could be partly alleviated by exogenous supply of deoxynucleosides. Our results highlight the importance of autophagy for DNA synthesis, suggesting that autophagy may support cancer progression, at least in part, by facilitating tumour cell survival and fitness under replication stress, a feature shared by most malignancies. These findings have implications for better understanding of the role of autophagy in tumorigenesis, as well as for attempts to manipulate autophagy as an anti-tumour therapeutic strategy.", "doi": "10.1038/s41418-019-0403-9", "pmid": "31409894", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7206042"}, {"db": "pii", "key": "10.1038/s41418-019-0403-9"}], "notes": [], "created": "2026-08-20T08:49:10.122Z", "modified": "2026-08-20T08:49:10.290Z"}, {"entity": "publication", "iuid": "d6bbc17de3e64a09b388236a08042019", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d6bbc17de3e64a09b388236a08042019.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d6bbc17de3e64a09b388236a08042019"}}, "title": "Differential Activity of ATR and WEE1 Inhibitors in a Highly Sensitive Subpopulation of DLBCL Linked to Replication Stress.", "authors": [{"family": "Young", "given": "Lucy A", "initials": "LA"}, {"family": "O'Connor", "given": "Lenka Oplustil", "initials": "LO", "orcid": "0000-0003-1823-625X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02a4437fac7949f1a1ff5a5bb43db739.json"}}, {"family": "de Renty", "given": "Christelle", "initials": "C"}, {"family": "Veldman-Jones", "given": "Margaret H", "initials": "MH"}, {"family": "Dorval", "given": "Thierry", "initials": "T"}, {"family": "Wilson", "given": "Zena", "initials": "Z"}, {"family": "Jones", "given": "David R", "initials": "DR"}, {"family": "Lawson", "given": "Deborah", "initials": "D"}, {"family": "Odedra", "given": "Rajesh", "initials": "R"}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Reimer", "given": "Corinne", "initials": "C"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Lau", "given": "Alan", "initials": "A"}, {"family": "O'Connor", "given": "Mark J", "initials": "MJ", "orcid": "0000-0003-1823-625X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02a4437fac7949f1a1ff5a5bb43db739.json"}}], "type": "journal article", "published": "2019-07-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "79", "issue": "14", "pages": "3762-3775", "issn-l": "0008-5472"}, "abstract": "DNA damage checkpoint kinases ATR and WEE1 are among key regulators of DNA damage response pathways protecting cells from replication stress, a hallmark of cancer that has potential to be exploited for therapeutic use. ATR and WEE1 inhibitors are in early clinical trials and success will require greater understanding of both their mechanism of action and biomarkers for patient selection. Here, we report selective antitumor activity of ATR and WEE1 inhibitors in a subset of non-germinal center B-cell (GCB) diffuse large B-cell lymphoma (DLBCL) cell lines, characterized by high MYC protein expression and CDKN2A/B deletion. Activity correlated with the induction of replication stress, indicated by increased origin firing and retardation of replication fork progression. However, ATR and WEE1 inhibitors caused different amounts of DNA damage and cell death in distinct phases of the cell cycle, underlying the increased potency observed with WEE1 inhibition. ATR inhibition caused DNA damage to manifest as 53BP1 nuclear bodies in daughter G1 cells leading to G1 arrest, whereas WEE1 inhibition caused DNA damage and arrest in S phase, leading to earlier onset apoptosis. In vivo xenograft DLBCL models confirmed differences in single-agent antitumor activity, but also showed potential for effective ATR inhibitor combinations. Importantly, insights into the different inhibitor mechanisms may guide differentiated clinical development strategies aimed at exploiting specific vulnerabilities of tumor cells while maximizing therapeutic index. Our data therefore highlight clinical development opportunities for both ATR and WEE1 inhibitors in non-GCB DLBCL subtypes that represent an area of unmet clinical need. SIGNIFICANCE: ATR and WEE1 inhibitors demonstrate effective antitumor activity in preclinical models of DLBCL associated with replication stress, but new mechanistic insights and biomarkers of response support a differentiated clinical development strategy.", "doi": "10.1158/0008-5472.CAN-18-2480", "pmid": "31123088", "labels": [], "xrefs": [{"db": "pii", "key": "0008-5472.CAN-18-2480"}], "notes": [], "created": "2026-08-20T12:10:53.350Z", "modified": "2026-08-20T12:10:53.475Z"}]}