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

Vinay V. Eapen, Neal Sugawara, Michael Tsabar, Wei Hua Wu, James E. Haber

    Research output: Contribution to journalArticle

    85 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)4727-4740
    Number of pages14
    JournalMolecular and Cellular Biology
    Volume32
    Issue number22
    DOIs
    StatePublished - Nov 1 2012

    Fingerprint

    Nucleosomes
    Homologous Recombination
    DNA Damage
    Chromatin
    Saccharomyces cerevisiae
    Exonucleases
    Saccharomycetales
    Endonucleases
    DNA
    Histones
    Digestion
    Cell Cycle
    Phosphorylation
    In Vitro Techniques

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

    Cite this

    The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end resection and checkpoint deactivation. / Eapen, Vinay V.; Sugawara, Neal; Tsabar, Michael; Wu, Wei Hua; Haber, James E.

    In: Molecular and Cellular Biology, Vol. 32, No. 22, 01.11.2012, p. 4727-4740.

    Research output: Contribution to journalArticle

    Eapen, Vinay V. ; Sugawara, Neal ; Tsabar, Michael ; Wu, Wei Hua ; Haber, James E. / The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end resection and checkpoint deactivation. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 22. pp. 4727-4740.
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