Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair
<p>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) i...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Association for the Advancement of Science
2024
|
| _version_ | 1826317759219236864 |
|---|---|
| author | Yang, H Fouad, S Smith, P Bae, EY Ji, Y Lan, X Van Ess, A Buffa, FM Fischer, R Vendrell, I Kessler, BM D’Angiolella, V |
| author_facet | Yang, H Fouad, S Smith, P Bae, EY Ji, Y Lan, X Van Ess, A Buffa, FM Fischer, R Vendrell, I Kessler, BM D’Angiolella, V |
| author_sort | Yang, H |
| collection | OXFORD |
| description | <p>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.</p> |
| first_indexed | 2025-03-11T16:59:00Z |
| format | Journal article |
| id | oxford-uuid:62b13902-17fe-4dcb-afb4-bd586670aa09 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-03-11T16:59:00Z |
| publishDate | 2024 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:62b13902-17fe-4dcb-afb4-bd586670aa092025-03-06T11:04:25ZCyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repairJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:62b13902-17fe-4dcb-afb4-bd586670aa09EnglishSymplectic ElementsAmerican Association for the Advancement of Science2024Yang, HFouad, SSmith, PBae, EYJi, YLan, XVan Ess, ABuffa, FMFischer, RVendrell, IKessler, BMD’Angiolella, V<p>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.</p> |
| spellingShingle | Yang, H Fouad, S Smith, P Bae, EY Ji, Y Lan, X Van Ess, A Buffa, FM Fischer, R Vendrell, I Kessler, BM D’Angiolella, V Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair |
| title | Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair |
| title_full | Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair |
| title_fullStr | Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair |
| title_full_unstemmed | Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair |
| title_short | Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair |
| title_sort | cyclin f exo1 axis controls cell cycle dependent execution of double strand break repair |
| work_keys_str_mv | AT yangh cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT fouads cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT smithp cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT baeey cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT jiy cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT lanx cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT vanessa cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT buffafm cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT fischerr cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT vendrelli cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT kesslerbm cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair AT dangiolellav cyclinfexo1axiscontrolscellcycledependentexecutionofdoublestrandbreakrepair |