{"entity": "publication", "iuid": "e06251bc320840929b8cb305af8d23bd", "timestamp": "2026-08-22T07:47:51.101Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e06251bc320840929b8cb305af8d23bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e06251bc320840929b8cb305af8d23bd"}}, "title": "CDK12 controls transcription at damaged genes and prevents MYC-induced transcription-replication conflicts.", "authors": [{"family": "Curti", "given": "Laura", "initials": "L"}, {"family": "Rohban", "given": "Sara", "initials": "S"}, {"family": "Bianchi", "given": "Nicola", "initials": "N"}, {"family": "Croci", "given": "Ottavio", "initials": "O"}, {"family": "Andronache", "given": "Adrian", "initials": "A", "orcid": "0009-0002-6961-7829", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b275873bf4b476182129d79791ac659.json"}}, {"family": "Barozzi", "given": "Sara", "initials": "S"}, {"family": "Mattioli", "given": "Michela", "initials": "M"}, {"family": "Ricci", "given": "Fernanda", "initials": "F"}, {"family": "Pastori", "given": "Elena", "initials": "E"}, {"family": "Sberna", "given": "Silvia", "initials": "S"}, {"family": "Bellotti", "given": "Simone", "initials": "S"}, {"family": "Accialini", "given": "Anna", "initials": "A"}, {"family": "Ballarino", "given": "Roberto", "initials": "R", "orcid": "0000-0001-7812-0940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7885bdf463cf41538ea08a35898c1cae.json"}}, {"family": "Crosetto", "given": "Nicola", "initials": "N", "orcid": "0000-0002-3019-6978", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b1cef698ae749749b4017dbacb9e3db.json"}}, {"family": "Wade", "given": "Mark", "initials": "M"}, {"family": "Parazzoli", "given": "Dario", "initials": "D", "orcid": "0000-0001-8176-9775", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5e797a3ebe9546cc8a398d326dbe4b91.json"}}, {"family": "Campaner", "given": "Stefano", "initials": "S", "orcid": "0000-0003-4547-6849", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c47263351cdd41b4a2c3a95f0430a1ef.json"}}], "type": "journal article", "published": "2024-08-18", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "7100", "issn-l": "2041-1723"}, "abstract": "The identification of genes involved in replicative stress is key to understanding cancer evolution and to identify therapeutic targets. Here, we show that CDK12 prevents transcription-replication conflicts (TRCs) and the activation of cytotoxic replicative stress upon deregulation of the MYC oncogene. CDK12 was recruited at damaged genes by PARP-dependent DDR-signaling and elongation-competent RNAPII, to repress transcription. Either loss or chemical inhibition of CDK12 led to DDR-resistant transcription of damaged genes. Loss of CDK12 exacerbated TRCs in MYC-overexpressing cells and led to the accumulation of double-strand DNA breaks, occurring between co-directional early-replicating regions and transcribed genes. Overall, our data demonstrate that CDK12 protects genome integrity by repressing transcription of damaged genes, which is required for proper resolution of DSBs at oncogene-induced TRCs. This provides a rationale that explains both how CDK12 deficiency can promote tandem duplications of early-replicated regions during tumor evolution, and how CDK12 targeting can exacerbate replicative-stress in tumors.", "doi": "10.1038/s41467-024-51229-5", "pmid": "39155303", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11330984"}, {"db": "pii", "key": "10.1038/s41467-024-51229-5"}], "notes": [], "created": "2026-08-21T11:49:55.780Z", "modified": "2026-08-21T11:49:55.957Z"}