title: Enrichment of Cdk1-cyclins at DNA double-strand breaks stimulates Fun30 phosphorylation and DNA end resection.
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.
authors.affiliation: College of Life Sciences and Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 40072, China xfchen@whu.edu.cn.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Biophysics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Molecular ad Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: College of Life Sciences and Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 40072, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Life Sciences and Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 40072, China.
authors.forename: Shuangyi
authors.initials: S
authors.lastname: Zhu
authors.affiliation: College of Life Sciences and Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 40072, China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Molecular ad Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Alma
authors.initials: A
authors.lastname: Papusha
authors.affiliation: Department of Molecular ad Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Molecular ad Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Biochemistry and Biophysics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry and Biophysics, Yale University School of Medicine, New Haven, CT, USA patrick.sung@yale.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
authors.affiliation: Department of Molecular ad Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA gira@bcm.edu.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Ira
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C093749:CLB2 protein, S cerevisiae; C076558:CLB5 protein, S cerevisiae; D002843:Chromatin; D019926:Cyclin B; C074000:FUN30 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012694:Serine; D016203:CDC2 Protein Kinase