Histone H1 variant, H1R is involved in DNA damage response
Histone H1 variant, H1R is involved in DNA damage response
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DOI：
10.1016/j.dnarep.2007.05.003
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发表时间：
2007-11-01
期刊：
影响因子：
3.8
通讯作者：
Shinkai, Yoichi
中科院分区：
文献类型：
--
作者：
Hashimoto, Hideharu;Sonoda, Eiichiro;Shinkai, Yoichi
在酿酒酵母中，连接蛋白HHO1参与DNA修复。在高等真核生物中，连接蛋白H1存在多种变体，但它们在DNA损伤反应中的作用尚不清楚。为了解决这个问题，我们检测了缺乏特定H1变异的鸡DT40细胞对基因毒性药物的敏感性。在6个H1突变体中，只有H1R(-/-) DT40细胞对烷基化剂甲基甲磺酸盐（MMS）的敏感性增加。Rad54的失活并没有增强H1R（-/-）细胞对MMS的敏感性。H1R(-/-) DT40细胞还表现出：(i)基因靶向效率降低，（ii）姐妹染色单体交换受损，以及（iii）在G2期ir诱导的染色体畸变的积累，所有这些都表明H1R参与了rad54介导的同源重组（HR）途径。MMS处理后，细胞核中H1R的流动性下降，而不是H1L， i - scei产生的双链断裂的修复在H1R（-/-）细胞中不受影响。这表明H1R在染色体结构水平上整合到hr介导的修复途径中。总之，这些发现提供了第一个遗传证据，表明特定的H1变异在脊椎动物的DNA损伤反应中起着独特而重要的作用。(c) 2007 Elsevier B.V.版权所有
In Saccharomyces cerevisiae, the linker histone HHO1 is involved in DNA repair. In higher eukaryotes, multiple variants of linker histone H1 exist but their involvement in the DNA damage response is unknown. To address this issue, we examined sensitivity to genotoxic agents in chicken DT40 cells lacking specific H1 variants. Among the six H1 variant mutants, only H1R(-/-) DT40 cells exhibited increased sensitivity to the alkylating agent methyl-methanesulfon ate (MMS). The MMS sensitivity of H1R(-/-) cells was not enhanced by inactivation of Rad54. H1R(-/-) DT40 cells also exhibited: (i) a reduction in gene targeting efficiencies, (ii) impaired sister chromatid exchange, and (iii) an accumulation of IR-induced chromosomal aberrations at the G2 phase, all of which indicate the involvement of H1R in the Rad54-mediated homologous recombination (HR) pathway The mobility of H1R but not H1L in the nucleus decreased after MMS treatment and the repair of double-stranded breaks generated by I-SceI was unaffected in H1R(-/-) cells, suggesting that H1R integrates into HR-mediated repair pathways at the chromosome structure level. Together, these findings provide the first genetic evidence that a specific H1 variant plays a unique and important role in the DNA damage response in vertebrates. (c) 2007 Elsevier B.V. All rights reserved.