Enrichment of Cdk1-cyclins at DNA double-strand breaks stimulates Fun30 phosphorylation and DNA end resection

Xuefeng Chen, Hengyao Niu, Yang Yu, Jingjing Wang, Shuangyi Zhu, Jianjie Zhou, Alma Papusha, Dandan Cui, Xuewen Pan, Youngho Kwon, Patrick Sung, Grzegorz Ira

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

DNA double-strand breaks (DSBs) are one of the most cytotoxic types of DNA lesion challenging genome integrity. The activity of cyclin-dependent kinase Cdk1 is essential for DSB repair by homologous recombination and for DNA damage signaling. Here we identify the Fun30 chromatin remodeler as a new target of Cdk1. Fun30 is phosphorylated by Cdk1 on Serine 28 to stimulate its functions in DNA damage response including resection of DSB ends. Importantly, Cdk1-dependent phosphorylation of Fun30-S28 increases upon DNA damage and requires the recruitment of Fun30 to DSBs, suggesting that phosphorylation increases in situ at the DNA damage. Consistently, we find that Cdk1 and multiple cyclins become highly enriched at DSBs and that the recruitment of Cdk1 and cyclins Clb2 and Clb5 ensures optimal Fun30 phosphorylation and checkpoint activation. We propose that the enrichment of Cdk1-cyclin complexes at DSBs serves as a mechanism for enhanced targeting and modulating of the activity of DNA damage response proteins.

Original languageEnglish (US)
Pages (from-to)2742-2753
Number of pages12
JournalNucleic acids research
Volume44
Issue number6
DOIs
StatePublished - Jan 21 2016
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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