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异染色质蛋白1在DNA修复过程中的功能。

Function of heterochromatin protein 1 during DNA repair.

作者信息

Bártová Eva, Malyšková Barbora, Komůrková Denisa, Legartová Soňa, Suchánková Jana, Krejčí Jana, Kozubek Stanislav

机构信息

Institute of Biophysics of the Czech Academy of Sciences, v.v.i., Královopolská 135, 612 65, Brno, Czech Republic.

出版信息

Protoplasma. 2017 May;254(3):1233-1240. doi: 10.1007/s00709-017-1090-3. Epub 2017 Feb 24.

Abstract

This review focuses on the function of heterochromatin protein HP1 in response to DNA damage. We specifically outline the regulatory mechanisms in which HP1 and its interacting partners are involved. HP1 protein subtypes (HP1α, HP1β, and HP1γ) are the main components of constitutive heterochromatin, and HP1α and HP1β in particular are responsible for heterochromatin maintenance. The recruitment of these proteins to DNA lesions is also important from the perspective of proper DNA repair mechanisms. For example, HP1α is necessary for the binding of the main DNA damage-related protein 53BP1 at DNA repair foci, which are positive not only for the HP1α protein but also for the RAD51 protein, a component of DNA repair machinery. The HP1β protein also appears in monomeric form in DNA lesions together with the evolutionarily well-conserved protein called proliferating cell nuclear antigen (PCNA). The role of HP1 in DNA lesions is also mediated via the Kap1 transcription repressor. Taken together, these results indicate that the function of HP1 after DNA injury depends strongly on the kinetics of other DNA repair-related factors and their post-translational modifications, such as the phosphorylation of Kap-1.

摘要

本综述聚焦于异染色质蛋白HP1在应对DNA损伤时的功能。我们详细阐述了HP1及其相互作用伙伴所涉及的调控机制。HP1蛋白亚型(HP1α、HP1β和HP1γ)是组成型异染色质的主要成分,尤其是HP1α和HP1β负责异染色质的维持。从适当的DNA修复机制角度来看,将这些蛋白招募至DNA损伤位点也很重要。例如,HP1α对于主要的DNA损伤相关蛋白53BP1在DNA修复位点的结合是必需的,这些位点不仅对HP1α蛋白呈阳性,而且对DNA修复机制的组成成分RAD51蛋白也呈阳性。HP1β蛋白在DNA损伤位点也以单体形式与一种名为增殖细胞核抗原(PCNA)的进化上高度保守的蛋白一同出现。HP1在DNA损伤中的作用还通过Kap1转录抑制因子介导。综上所述,这些结果表明DNA损伤后HP1的功能在很大程度上取决于其他DNA修复相关因子的动力学及其翻译后修饰,如Kap-1的磷酸化。

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