DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites.

DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites.
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DOI:
10.1083/jcb.201704028
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发表时间:
2018-02-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Richly H
Richly H
中科院分区:
其他
文献类型:
--
作者:
Chitale S;Richly H

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核糖核酸内切酶DICER在紫外线照射后的病变识别过程中促进染色质去浓缩。Chitale和rich表明DICER介导甲基转移酶MMSET的募集,MMSET催化组蛋白H4在赖氨酸20位点的二甲基化,并促进核苷酸切除修复因子XPA的募集。紫外线(UV)照射触发DNA修复因子募集到损伤部位和组蛋白标记沉积作为DNA损伤反应的一部分。清除紫外线照射引起的DNA损伤的主要DNA修复途径是核苷酸切除修复(NER)。我们之前已经证明,核糖核酸内切酶DICER在NER的全球基因组分支的病变识别过程中促进染色质去浓缩。在这里,我们报道DICER介导甲基转移酶MMSET募集到DNA损伤位点。我们发现MMSET是高效NER所必需的,并且它在赖氨酸20 (H4K20me2)处催化组蛋白H4的二甲基化。DNA损伤位点的H4K20me2促进NER因子XPA的募集。因此,我们的工作为在NER的全球基因组分支的病变识别过程中依赖h4k20me2的XPA募集机制提供了证据。
The endoribonuclease DICER facilitates chromatin decondensation during lesion recognition following UV exposure. Chitale and Richly show that DICER mediates the recruitment of the methyltransferase MMSET, which catalyzes the dimethylation of histone H4 at lysine 20 and facilitates the recruitment of the nucleotide excision repair factor XPA. Ultraviolet (UV) irradiation triggers the recruitment of DNA repair factors to the lesion sites and the deposition of histone marks as part of the DNA damage response. The major DNA repair pathway removing DNA lesions caused by exposure to UV light is nucleotide excision repair (NER). We have previously demonstrated that the endoribonuclease DICER facilitates chromatin decondensation during lesion recognition in the global-genomic branch of NER. Here, we report that DICER mediates the recruitment of the methyltransferase MMSET to the DNA damage site. We show that MMSET is required for efficient NER and that it catalyzes the dimethylation of histone H4 at lysine 20 (H4K20me2). H4K20me2 at DNA damage sites facilitates the recruitment of the NER factor XPA. Our work thus provides evidence for an H4K20me2-dependent mechanism of XPA recruitment during lesion recognition in the global-genomic branch of NER.
翻译后组蛋白修饰在核苷酸切除修复中的影响。
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