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酿酒酵母染色质重塑因子 Fun30 调节 DNA 末端切除和检验点失活。

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

机构信息

Department of Biology, Rosenstiel Basic Medical Sciences Center, Brandeis University, Waltham, Massachusetts, USA.

出版信息

Mol Cell Biol. 2012 Nov;32(22):4727-40. doi: 10.1128/MCB.00566-12. Epub 2012 Sep 24.

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.

摘要

Fun30 是芽殖酵母中的 Swi2/Snf2 同源物,已被证明可在体外和体内重塑染色质。我们报告说 Fun30 通过促进双链断裂 (DSB) 末端的 5'到 3'切除,显然通过促进核小体结合 DNA 的外切酶消化,在同源重组中发挥关键作用,这些 DNA 紧邻 DSB。Fun30 被招募到 HO 内切酶诱导的 DSB 中,并在 Exo1 依赖性和 Sgs1 依赖性切除途径中发挥作用。FUN30 的缺失会将 5'到 3'切除的速度从 4 kb/h 降低到约 1.2 kb/h。我们还发现,DNA 损伤诱导的组蛋白 H2A-S129(γ-H2AX)磷酸化会降低切除率,并且 Fun30 与未磷酸化的 H2A-S129 的核小体优先相互作用。Fun30 不需要同源重组的后期步骤。像它的同源物 Rdh54/Tid1 一样,Fun30 是允许具有未修复 DSB 的 DNA 损伤检查点阻滞细胞适应并恢复细胞周期进程所必需的。

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本文引用的文献

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