{"entity": "researcher", "timestamp": "2026-08-20T20:53:11.640Z", "family": "Hynds", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-2170-8791", "affiliations": ["Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London, UK.", "Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d363c63598224cb0bd24dffc46d0d3eb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d363c63598224cb0bd24dffc46d0d3eb"}}, "publications": [{"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": "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"}]}