Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair-Reference-Cited by-同舟云学术

Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair

Published:2024-08-09 Issue:32 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Yang Hongbin¹^ORCID,Fouad Shahd¹,Smith Paul¹²^ORCID,Bae Eun Young¹^ORCID,Ji Yu¹^ORCID,Lan Xinhui¹²^ORCID,Van Ess Ava¹²^ORCID,Buffa Francesca M.¹³⁴^ORCID,Fischer Roman⁵⁶^ORCID,Vendrell Iolanda⁵⁶^ORCID,Kessler Benedikt M.⁵⁶^ORCID,D’Angiolella Vincenzo¹²^ORCID

Affiliation:

1. MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.

2. Edinburgh Cancer Research, CRUK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK.

3. Medical Science Division, University of Oxford, Oxford OX3 7DQ, UK.

4. Department of Computing Sciences and the Bocconi Institute for Data Science and Analytics, Bocconi University, Milan, Italy.

5. Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.

6. Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK.

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 cyclin F in cell cycle–dependent DSB repair. We show that SCF cyclin F –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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.ado0636

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