title: Cyclin-dependent kinase-dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double-strand break resection.
abstract: DNA double-strand breaks (DSBs) are repaired by two distinct pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ). NHEJ includes two pathways, that is, precise and imprecise end joining. We found that Lif1, a component of the DNA ligase IV complex in Saccharomyces cerevisiae, was phosphorylated by cyclin-dependent kinase (CDK) at Ser261 during the S to G2 phase but not during G1 phase. This phosphorylation was required for efficient NHEJ in G2/M cells, rather than in G1 cells. It also promotes the stable binding of Lif1 protein to DSBs, specifically in G2/M-arrested cells, which shows the resection of DSB ends. Thus, Lif1 phosphorylation plays a critical role in a certain type of imprecise NHEJ accompanied by DSB end resection and micro-homology. Lif1 phosphorylation at Ser261 is probably involved in micro-homology-dependent end joining associated with producing single-stranded DSB ends that are formed by Sae2 as early intermediates in the HR pathway. CDK-dependent modification of the NHEJ pathway might make DSB ends compatible for NHEJ and thus prevent competition between HR and NHEJ in hierarchy on the choice of DSB repair pathways.
authors.affiliation: Department of Integrated Protein Functions, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Terasawa
authors.forename: Daichi
authors.initials: D
authors.lastname: Iwasaki
authors.forename: Mika
authors.initials: M
authors.lastname: Higashide
authors.forename: Miki
authors.initials: M
authors.lastname: Shinohara
mesh_terms: D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D010766:Phosphorylation; D059767:Recombinational DNA Repair; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C114091:LIF1 protein, S cerevisiae; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; D004720:Endonucleases