A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast.
A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast.
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DOI：
10.1093/nar/gkn311
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发表时间：
2008-06
影响因子：
14.9
通讯作者：
Smerdon MJ
中科院分区：
文献类型：
--
作者：
Nag R;Gong F;Fahy D;Smerdon MJ
组蛋白H3和H4的特定DNA接触处的单个氨基酸变化在酵母中产生SWI/SNF非依赖性（Sin）突变体。我们已经分析了组蛋白H4的R45处的Sin突变对UV照射后细胞存活、核苷酸切除修复（NER）和染色质结构的影响。我们发现，这种突变使酵母细胞更耐紫外线损伤，并提高NER在特定的染色质位点。在转录沉默的HML，抑制GAL 10和组成型活性RPB 2基因座，H4 R45突变体表现出增强的修复UV诱导的环丁烷嘧啶二聚体（CPD）相比，野生型（wt）。然而，H4 R45突变不会增加NER基因的转录，破坏HML基因座的转录沉默或改变GAL 10基因座中的抑制。我们进一步表明，H4 R45 C突变增加了染色质中的核小体DNA对外源核酸酶的可及性，并可能加速NER期间的核小体重排。总之，我们的结果表明，在Sin突变体中观察到的修复增加是由突变引起的染色质景观改变的直接影响，这表明保守组蛋白残基的这种微妙变化可以影响染色质中DNA修复因子的可及性。
Single amino acid changes at specific DNA contacts of histones H3 and H4 generate SWI/SNF-independent (Sin) mutants in yeast. We have analyzed the effect of the Sin mutation at R45 of histone H4 on cell survival following UV irradiation, nucleotide excision repair (NER) and chromatin structure. We find that this mutation renders yeast cells more resistant to UV damage and enhances NER at specific chromatin loci. In the transcriptionally silent HML, repressed GAL10 and the constitutively active RPB2 loci, H4 R45 mutants exhibit enhanced repair of UV-induced cyclobutane pyrimidine dimers (CPDs) compared to wild-type (wt). However, the H4 R45 mutation does not increase the transcription of NER genes, disrupt transcriptional silencing of the HML locus or alter repression in the GAL10 locus. We have further shown that the H4 R45C mutation increases the accessibility of nucleosome DNA in chromatin to exogenous nucleases and may expedite nucleosome rearrangements during NER. Taken together, our results indicate that the increased repair observed in Sin mutants is a direct effect of the altered chromatin landscape caused by the mutation, suggesting that such subtle changes in the conserved histone residues can influence the accessibility of DNA repair factors in chromatin.
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