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Histone lysine modifying enzymes and their critical roles in DNA double-strand break repair
DNA Repair ( IF 3.8 ) Pub Date : 2021-08-12 , DOI: 10.1016/j.dnarep.2021.103206
Jun Zhang 1 , Xiaopeng Lu 1 , Sara MoghaddamKohi 1 , Lei Shi 2 , Xingzhi Xu 3 , Wei-Guo Zhu 1
Affiliation  

Cells protect the integrity of the genome against DNA double-strand breaks through several well-characterized mechanisms including nonhomologous end-joining repair, homologous recombination repair, microhomology-mediated end-joining and single-strand annealing. However, aberrant DNA damage responses (DDRs) lead to genome instability and tumorigenesis. Clarification of the mechanisms underlying the DDR following lethal damage will facilitate the identification of therapeutic targets for cancer. Histones are small proteins that play a major role in condensing DNA into chromatin and regulating gene function. Histone modifications commonly occur in several residues including lysine, arginine, serine, threonine and tyrosine, which can be acetylated, methylated, ubiquitinated and phosphorylated. Of these, lysine modifications have been extensively explored during DDRs. Here, we focus on discussing the roles of lysine modifying enzymes involved in acetylation, methylation, and ubiquitination during the DDR. We provide a comprehensive understanding of the basis of potential epigenetic therapies driven by histone lysine modifications.



中文翻译:

组蛋白赖氨酸修饰酶及其在 DNA 双链断裂修复中的关键作用

细胞通过几种已明确表征的机制保护基因组的完整性免受 DNA 双链断裂,包括非同源末端连接修复、同源重组修复、微同源介导的末端连接和单链退火。然而,异常的 DNA 损伤反应 (DDR) 会导致基因组不稳定和肿瘤发生。阐明致死性损伤后 DDR 的潜在机制将有助于确定癌症的治疗靶点。组蛋白是一种小蛋白质,在将 DNA 浓缩成染色质和调节基因功能方面发挥着重要作用。组蛋白修饰通常发生在几个残基中,包括赖氨酸、精氨酸、丝氨酸、苏氨酸和酪氨酸,它们可以被乙酰化、甲基化、泛素化和磷酸化。这些,在 DDR 期间已广泛探索了赖氨酸修饰。在这里,我们将重点讨论赖氨酸修饰酶在 DDR 中参与乙酰化、甲基化和泛素化的作用。我们全面了解由组蛋白赖氨酸修饰驱动的潜在表观遗传疗法的基础。

更新日期:2021-08-16
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