Cyclin F-EXO1 axis controls cell cycle-dependent execution of double-strand break repair.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39121215.
- Also identified by DOI 10.1126/sciadv.ado0636 and PMC identifier 11313846.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Ubiquitination is a crucial posttranslational modification required for the proper repair of DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). DSBs are mainly repaired through homologous recombination (HR) when template DNA is present and nonhomologous end joining (NHEJ) in its absence. In addition, microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA) provide backup DSBs repair pathways. However, the mechanisms controlling their use remain poorly understood. By using a high-resolution CRISPR screen of the ubiquitin system after IR, we systematically uncover genes required for cell survival and elucidate a critical role of the E3 ubiquitin ligase SCF<sup>cyclin F</sup> in cell cycle-dependent DSB repair. We show that SCF<sup>cyclin F</sup>-mediated EXO1 degradation prevents DNA end resection in mitosis, allowing MMEJ to take place. Moreover, we identify a conserved cyclin F recognition motif, distinct from the one used by other cyclins, with broad implications in cyclin specificity for cell cycle control.
Medical subject headings
- DNA Breaks, Double-Stranded
- Cell Cycle
- DNA Repair
- Exodeoxyribonucleases
- Cyclins