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The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end resection and checkpoint deactivation.

http://www.ncbi.nlm.nih.gov/pubmed/23007155

Fun30 is a Swi2/Snf2 homolog in budding yeast that has been shown to remodel chromatin both in vitro and in vivo. We report that Fun30 plays a key role in homologous recombination, by facilitating 5'-to-3' resection of double-strand break (DSB) ends, apparently by facilitating exonuclease digestion of nucleosome-bound DNA adjacent to the DSB. Fun30 is recruited to an HO endonuclease-induced DSB and acts in both the Exo1-dependent and Sgs1-dependent resection pathways. Deletion of FUN30 slows the rate of 5'-to-3' resection from 4 kb/h to about 1.2 kb/h. We also found that the resection rate is reduced by DNA damage-induced phosphorylation of histone H2A-S129 (γ-H2AX) and that Fun30 interacts preferentially with nucleosomes in which H2A-S129 is not phosphorylated. Fun30 is not required for later steps in homologous recombination. Like its homolog Rdh54/Tid1, Fun30 is required to allow the adaptation of DNA damage checkpoint-arrested cells with an unrepaired DSB to resume cell cycle progression.

Pubmed ID: 23007155 RIS Download

Mesh terms: Adaptation, Physiological | Cell Cycle Checkpoints | Chromatin | Chromatin Assembly and Disassembly | DNA Breaks, Double-Stranded | DNA, Fungal | Exodeoxyribonucleases | Histones | Homologous Recombination | Nucleosomes | Phosphorylation | RecQ Helicases | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Sequence Homology, Amino Acid | Signal Transduction | Transcription Factors

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Associated grants

  • Agency: NCI NIH HHS, Id: 1K22CA122453
  • Agency: NIGMS NIH HHS, Id: GM20056
  • Agency: NIGMS NIH HHS, Id: GM61766
  • Agency: NIGMS NIH HHS, Id: R37 GM020056

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