WRAP53 β调控DNA损伤修复进展
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四川大学华西临床医学院,口腔疾病研究国家重点实验室,口腔疾病研究国家重点实验室,口腔疾病研究国家重点实验室

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国家自然科学基金面上项目(81172579)


Progress of WRAP53 β Regulating DNA Damage Repair
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West China School of Medicine,Sichuan University,State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China,State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China,State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China

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This work was supported by a grant from The National Natural Science Foundation of China (81172579)

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    摘要:

    WRAP53 β是一种具有WD40结构域的蛋白质,在维护卡哈尔体稳定、RNA剪接、端粒延伸等方面起着至关重要的作用.WRAP53 β功能紊乱与先天性角化不良、肿瘤、进行性脊髓性肌萎缩、过早老化等疾病有关.近两年研究发现WRAP53 β是DNA双链断裂修复(DSBs)的一个重要支架蛋白,它以一种依赖于ATM、H2AX、MDC1的方式被募集至损伤位点并磷酸化,其WD40结构域可募集泛素E3连接酶RNF8,将DSBs位点附近的组蛋白H2AX泛素化,促进下游修复因子的聚集,引起DNA损伤后的修复作用.为此,我们重点综述了现阶段WRAP53 β在DNA损伤修复方面的具体作用及 机制.

    Abstract:

    WRAP53 beta, a protein with a WD40 domain, plays an essential role in the maintenance of Cajal body stability, RNA splicing, and telomere elongation. WRAP53 β dysfunction is related to dyskeratosis congenita, tumor, progressive spinal muscular atrophy, premature aging and other diseases. Recent studies have found that WRAP53 β is an important scaffold protein essential for DNA double strand break repair (DSBs). It can be recruited to DNA damage sites in a H2AX, ATM and MDC1-dependent manner and phosphorylated by ATM. Then the phosphorylated WRAP53 β recruits ubiquitin E3 ligase RNF8 through its WD40 domain leading to histone H2AX ubiquitination, and further aggregation of downstream repair factors for DNA damage repair. In this review, we summarize the recent advances in the specific role and underlying mechanisms of WRAP53 β in the repair of DNA damages.

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姚羽菲,崔博淼,肖丽英,李燕. WRAP53 β调控DNA损伤修复进展[J].生物化学与生物物理进展,2018,45(6):613-620

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历史
  • 收稿日期:2017-11-08
  • 最后修改日期:2018-04-03
  • 接受日期:2018-04-09
  • 在线发布日期: 2018-04-10
  • 出版日期: 2018-06-20