Trypanosomal histone γH2A and the DNA damage response
Trypanosomal histone γH2A and the DNA damage response
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DOI：
10.1016/j.molbiopara.2012.01.008
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发表时间：
2012-05-01
影响因子：
1.5
通讯作者：
Horn, David
中科院分区：
文献类型：
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作者：
Glover, Lucy;Horn, David
DNA损伤和修复锥虫的影响毒力，耐药性和抗原变异，但目前，很少有人知道这些不同的原生动物的DNA损伤反应或细胞周期检查点。真核生物中DNA损伤的最早标志物之一是γ H2A（X），一种丝氨酸磷酸化的组蛋白H2A（变体）。在这里，我们报告的γ H2A在布氏锥虫的识别和初步表征。我们鉴定了复制依赖性组蛋白H2A内的Thr（130）作为候选磷酸化位点，并发现这种锥虫γ H2A的丰度在体内响应于DNA损伤而增加。核γ H2A焦点标记推定的自然复制叉失速的网站，大范围核酸酶诱导的DNA双链断裂的网站和甲基甲磺酸诱导的DNA损伤的网站。天然存在的和大范围核酸酶诱导的γ H2A和RAD 51双阳性修复灶通常发现于S期或G（2）核中。这些结果将具有不寻常的组蛋白修饰基序的锥虫γ H2A与DNA损伤传感和有丝分裂检查点信号联系起来。(C)2012爱思唯尔有限公司版权所有。
DNA damage and repair in trypanosomatids impacts virulence, drug resistance and antigenic variation but, currently, little is known about DNA damage responses or cell cycle checkpoints in these divergent protozoa. One of the earliest markers of DNA damage in eukaryotes is gamma H2A(X), a serine phosphorylated histone H2A (variant). Here, we report the identification and initial characterization of gamma H2A in Trypanosoma brucei. We identified Thr(130) within the replication-dependent histone H2A as a candidate phosphorylation site and found that the abundance of this trypanosomal gamma H2A increased in vivo in response to DNA damage. Nuclear gamma H2A foci mark the sites of putative natural replication fork stalling, sites of meganuclease-induced DNA double strand breaks and sites of methyl methanesulphonate-induced DNA damage. Naturally occurring and meganuclease-induced gamma H2A and RAD51 double-positive repair foci are typically found in S-phase or G(2) nuclei. The results link trypanosomal gamma H2A, with an unusual histone modification motif, to DNA damage sensing and mitotic checkpoint signaling. (C) 2012 Elsevier B.V. All rights reserved.