A role for Saccharomyces cerevisiae histone H2A in DNA repair
A role for Saccharomyces cerevisiae histone H2A in DNA repair
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DOI：
10.1038/35050000
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发表时间：
2000-12-21
期刊：
影响因子：
64.8
通讯作者：
Jackson, SP
中科院分区：
文献类型：
--
作者：
Downs, JA;Lowndes, NF;Jackson, SP
组蛋白与真核细胞核 DNA 结合并压缩形成染色质。染色质的基本单位是核小体，由 146 个碱基对的 DNA 组成，缠绕在四个核心组蛋白 (1)、H2A、H2B、H3 和 H4 中各两个组蛋白周围。染色质结构及其调控对于转录和 DNA 复制非常重要(2-4)。因此，我们认为 DNA 损伤信号传导和修复成分也可能调节染色质结构。在这里，我们鉴定了酿酒酵母核心组蛋白 H2A 羧基末端的保守基序，其中包含磷脂酰肌醇-3-OH 激酶相关激酶 (PIKK) 的共有磷酸化位点。该基序对于在产生 DNA 双链断裂的试剂存在下的生存很重要，并且该基序响应 DNA 损伤的磷酸化依赖于 PIKK 家族成员 Mec1。该基序对于 Mec1 依赖性细胞周期或对 DNA 损伤的转录反应不是必需的，但对于通过非同源末端连接进行有效的 DNA 双链断裂修复是必需的。此外，该基序在确定高级染色质结构中也发挥着作用。因此，核心组蛋白对 DNA 损伤的磷酸化可能会导致染色质结构的改变，从而促进 DNA 修复。
Histone proteins associate with and compact eukaryotic nuclear DNA to form chromatin. The basic unit of chromatin is the nucleosome, which is made up of 146 base pairs of DNA wrapped around two of each of four core histones(1), H2A, H2B, H3 and H4. Chromatin structure and its regulation are important in transcription and DNA replication(2-4). We therefore thought that DNA-damage signalling and repair components might also modulate chromatin structure. Here we have characterized a conserved motif in the carboxy terminus of the core histone H2A from Saccharomyces cerevisiae that contains a consensus phosphorylation site for phosphatidylinositol-3-OH kinase related kinases (PIKKs). This motif is important for survival in the presence of agents that generate DNA double-strand breaks, and the phosphorylation of this motif in response to DNA damage is dependent on the PIKK family member Mec1. The motif is not necessary for Mec1-dependent cell-cycle or transcriptional responses to DNA damage, but is required for efficient DNA double-strand break repair by non-homologous end joining. In addition, the motif has a role in determining higher order chromatin structure. Thus, phosphorylation of a core histone in response to DNA damage may cause an alteration of chromatin structure that facilitates DNA repair.