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Cdk1 restrains NHEJ through phosphorylation of XRCC4-like factor Xlf1

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journal contribution
posted on 2023-06-08, 19:37 authored by Pierre Hentges, Helen Rachel Waller, Clara C Reis, Miguel Godinho Ferreira, Aidan DohertyAidan Doherty
Eukaryotic cells use two principal mechanisms for repairing DNA double-strand breaks (DSBs): homologous recombination (HR) and nonhomologous end-joining (NHEJ). DSB repair pathway choice is strongly regulated during the cell cycle. Cyclin-dependent kinase 1 (Cdk1) activates HR by phosphorylation of key recombination factors. However, a mechanism for regulating the NHEJ pathway has not been established. Here, we report that Xlf1, a fission yeast XLF ortholog, is a key regulator of NHEJ activity in the cell cycle. We show that Cdk1 phosphorylates residues in the C terminus of Xlf1 over the course of the cell cycle. Mutation of these residues leads to the loss of Cdk1 phosphorylation, resulting in elevated levels of NHEJ repair in vivo. Together, these data establish that Xlf1 phosphorylation by Cdc2Cdk1 provides a molecular mechanism for downregulation of NHEJ in fission yeast and indicates that XLF is a key regulator of end-joining processes in eukaryotic organisms.

Funding

Cell cycle regulation of the NHEJ DNA double-strand break repair pathway in eukaryotes; G1554; BBSRC; BB/M004236/1

Understanding the cellular regulation of the NHEJ double-break repair pathway; R3KJ; Cancer Research UK; C1470/A12430

History

Publication status

  • Published

File Version

  • Published version

Journal

Cell Reports

ISSN

2211-1247

Publisher

Elsevier Inc.

Issue

6

Volume

9

Page range

2011-2017

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-01-20

First Open Access (FOA) Date

2015-01-20

First Compliant Deposit (FCD) Date

2015-01-19

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