酿酒酵母Rad16介导高效全基因组核苷酸切除修复所需的紫外线依赖性组蛋白H3乙酰化。
Saccharomyces cerevisiae Rad16 mediates ultraviolet-dependent histone H3 acetylation required for efficient global genome nucleotide-excision repair.
作者信息
Teng Yumin, Liu Hairong, Gill Hefin W, Yu Yachuan, Waters Raymond, Reed Simon H
机构信息
Department of Pathology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
出版信息
EMBO Rep. 2008 Jan;9(1):97-102. doi: 10.1038/sj.embor.7401112. Epub 2007 Nov 9.
Abstract
In yeast, global genome nucleotide-excision repair (GG-NER) requires a protein complex containing Rad7 and Rad16. Rad16 is a member of the switch/sucrose nonfermentable superfamily, and it is presumed that chromatin remodelling is its primary function during repair. We show that RAD16 is required for ultraviolet-dependent hyperacetylation of histone H3 (Lys 9 and Lys 14) at the MFA2 promoter and throughout the genome. The yeast repressor complex Ssn6-Tup1 represses many genes including MFA2. TUP1 deletion results in constitutive hyperacetylation of histone H3, nucleosome disruption and derepression of gene transcription in Tup1-regulated genes. GG-NER in the MFA2 promoter proceeds more rapidly in tup1Delta alpha-cells compared with wild type, even when transcription is inhibited. We show that elevated histone H3 acetylation levels in the MFA2 promoter in tup1Delta alpha-cells result in Rad7- and Rad16-independent GG-NER, and that Rad16 mediates the ultraviolet-induced acetylation of histone H3, necessary for efficient GG-NER.
摘要
在酵母中，全基因组核苷酸切除修复（GG-NER）需要一种包含Rad7和Rad16的蛋白质复合物。Rad16是开关/蔗糖非发酵超家族的成员，据推测染色质重塑是其在修复过程中的主要功能。我们发现，RAD16是MFA2启动子及整个基因组中组蛋白H3（赖氨酸9和赖氨酸14）紫外线依赖性超乙酰化所必需的。酵母阻遏复合物Ssn6-Tup1可抑制包括MFA2在内的许多基因。TUP1缺失导致组蛋白H3组成型超乙酰化、核小体破坏以及Tup1调控基因的转录去抑制。与野生型相比，即使在转录受到抑制时，MFA2启动子中的GG-NER在tup1Δα细胞中也进行得更快。我们发现，tup1Δα细胞中MFA2启动子中组蛋白H3乙酰化水平升高导致了不依赖Rad7和Rad16的GG-NER，并且Rad16介导了高效GG-NER所必需的紫外线诱导的组蛋白H3乙酰化。
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