{"entity": "researcher", "timestamp": "2026-08-20T20:44:30.920Z", "family": "Galarreta", "given": "Antonio", "initials": "A", "orcid": "0000-0003-2358-7927", "affiliations": ["Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/afa6e99550224076bf06615778479685.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/afa6e99550224076bf06615778479685"}}, "publications": [{"entity": "publication", "iuid": "8fc1536c887f4d47bc6908d65a43fca2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8fc1536c887f4d47bc6908d65a43fca2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8fc1536c887f4d47bc6908d65a43fca2"}}, "title": "Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.", "authors": [{"family": "Galarreta", "given": "Antonio", "initials": "A", "orcid": "0000-0003-2358-7927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afa6e99550224076bf06615778479685.json"}}, {"family": "Valledor", "given": "Pablo", "initials": "P"}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O"}, {"family": "Lecona", "given": "Emilio", "initials": "E", "orcid": "0000-0002-1687-2562", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/16cf65e3590d430bbd2f3fbf1fddfa39.json"}}], "type": "journal article", "published": "2021-08-16", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "22", "issue": "16", "issn-l": null}, "abstract": "Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in the faithful duplication of the genetic information. Among other functions, ubiquitination and SUMOylation serve as signals for the extraction of factors from chromatin by the AAA ATPase VCP. In addition to the regulation of DNA replication initiation and elongation, we now know that ubiquitination mediates the disassembly of the replisome after DNA replication termination, a process that is essential to preserve genomic stability. Here, we review the recent evidence showing how active DNA replication restricts replisome ubiquitination to prevent the premature disassembly of the DNA replication machinery. Ubiquitination also mediates the removal of the replisome to allow DNA repair. Further, we discuss the interplay between ubiquitin-mediated replisome disassembly and the activation of CDK1 that is required to set up the transition from the S phase to mitosis. We propose the existence of a ubiquitin-CDK1 relay, where the disassembly of terminated replisomes increases CDK1 activity that, in turn, favors the ubiquitination and disassembly of more replisomes. This model has important implications for the mechanism of action of cancer therapies that induce the untimely activation of CDK1, thereby triggering premature replisome disassembly and DNA damage.", "doi": "10.3390/ijms22168796", "pmid": "34445496", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8395760"}, {"db": "pii", "key": "ijms22168796"}], "notes": [], "created": "2026-08-20T13:41:23.797Z", "modified": "2026-08-20T13:41:23.869Z"}, {"entity": "publication", "iuid": "a9924f0b5427486390e3b236da64b749", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a9924f0b5427486390e3b236da64b749.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a9924f0b5427486390e3b236da64b749"}}, "title": "Widespread displacement of DNA- and RNA-binding factors underlies toxicity of arginine-rich cell-penetrating peptides.", "authors": [{"family": "Lafarga", "given": "Vanesa", "initials": "V"}, {"family": "Sirozh", "given": "Oleksandra", "initials": "O"}, {"family": "D\u00edaz-L\u00f3pez", "given": "Irene", "initials": "I"}, {"family": "Galarreta", "given": "Antonio", "initials": "A", "orcid": "0000-0003-2358-7927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afa6e99550224076bf06615778479685.json"}}, {"family": "Hisaoka", "given": "Misaru", "initials": "M"}, {"family": "Zarzuela", "given": "Eduardo", "initials": "E"}, {"family": "Boskovic", "given": "Jasminka", "initials": "J"}, {"family": "Jovanovic", "given": "Bogdan", "initials": "B"}, {"family": "Fernandez-Leiro", "given": "Rafael", "initials": "R", "orcid": "0000-0002-7941-0357", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/082cd4d551754cbd91af9bcf249a3912.json"}}, {"family": "Mu\u00f1oz", "given": "Jaime", "initials": "J"}, {"family": "Stoecklin", "given": "Georg", "initials": "G", "orcid": "0000-0001-9284-9834", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65fee664b61c42b1ad51358fe34e2608.json"}}, {"family": "Ventoso", "given": "Iv\u00e1n", "initials": "I"}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab1f07900e6e466d83763e5fe0020ed6.json"}}], "type": "journal article", "published": "2021-07-01", "journal": {"title": "EMBO J.", "issn": "1460-2075", "volume": "40", "issue": "13", "pages": "e103311", "issn-l": "0261-4189"}, "abstract": "Due to their capability to transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic lateral sclerosis (ALS) as a model of an arginine-rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA- and DNA-binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids, such as RNA transcription, translation, splicing and degradation, or DNA replication and repair, is impaired by the presence of the CPPs. Interestingly, the effects of (PR)n are fully mimicked by protamine, a small arginine-rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA- and DNA-binding factors from chromatin and mRNA accounts for the toxicity of arginine-rich CPPs, including those that have been recently associated with the onset of ALS.", "doi": "10.15252/embj.2019103311", "pmid": "33978236", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8246256"}], "notes": [], "created": "2026-08-20T12:51:31.926Z", "modified": "2026-08-20T12:51:32.043Z"}, {"entity": "publication", "iuid": "7760d431e3664f2d8e55416b641390f8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7760d431e3664f2d8e55416b641390f8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7760d431e3664f2d8e55416b641390f8"}}, "title": "USP7 limits CDK1 activity throughout the cell cycle.", "authors": [{"family": "Galarreta", "given": "Antonio", "initials": "A", "orcid": "0000-0003-2358-7927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/afa6e99550224076bf06615778479685.json"}}, {"family": "Valledor", "given": "Pablo", "initials": "P", "orcid": "0000-0001-8215-7914", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/311d8e1c65bf437f94e35fdb90453ebd.json"}}, {"family": "Ubieto-Capella", "given": "Patricia", "initials": "P"}, {"family": "Lafarga", "given": "Vanesa", "initials": "V"}, {"family": "Zarzuela", "given": "Eduardo", "initials": "E"}, {"family": "Mu\u00f1oz", "given": "Javier", "initials": "J", "orcid": "0000-0003-3288-3496", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0f5947eb1a88407097be793853f3b08c.json"}}, {"family": "Malumbres", "given": "Marcos", "initials": "M", "orcid": "0000-0002-0829-6315", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3da3462ae875499a98fda83ecb8406ac.json"}}, {"family": "Lecona", "given": "Emilio", "initials": "E", "orcid": "0000-0002-1687-2562", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/16cf65e3590d430bbd2f3fbf1fddfa39.json"}}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab1f07900e6e466d83763e5fe0020ed6.json"}}], "type": "journal article", "published": "2021-06-01", "journal": {"title": "EMBO J.", "issn": "1460-2075", "volume": "40", "issue": "11", "pages": "e99692", "issn-l": "0261-4189"}, "abstract": "Chemical inhibitors of the deubiquitinase USP7 are currently being developed as anticancer agents based on their capacity to stabilize P53. Regardless of this activity, USP7 inhibitors also generate DNA damage in a p53-independent manner. However, the mechanism of this genotoxicity and its contribution to the anticancer effects of USP7 inhibitors are still under debate. Here we show that, surprisingly, even if USP7 inhibitors stop DNA replication, they also induce a widespread activation of CDK1 throughout the cell cycle, which leads to DNA damage and is toxic for mammalian cells. In addition, USP7 interacts with the phosphatase PP2A and supports its active localization in the cytoplasm. Accordingly, inhibition of USP7 or PP2A triggers very similar changes of the phosphoproteome, including a widespread increase in the phosphorylation of CDK1 targets. Importantly, the toxicity of USP7 inhibitors is alleviated by lowering CDK1 activity or by chemical activation of PP2A. Our work reveals that USP7 limits CDK1 activity at all cell cycle stages, providing a novel mechanism that explains the toxicity of USP7 inhibitors through untimely activation of CDK1.", "doi": "10.15252/embj.201899692", "pmid": "33856059", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8167359"}], "notes": [], "created": "2026-08-20T12:51:30.021Z", "modified": "2026-08-20T12:51:30.253Z"}]}