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如何恢复 DNA 损伤应答中的染色质结构和功能——让伴侣蛋白发挥作用:2013 年 7 月 9 日在俄罗斯圣彼得堡举行的第 38 届欧洲生物化学学会联合会大会上发表。

How to restore chromatin structure and function in response to DNA damage--let the chaperones play: delivered on 9 July 2013 at the 38th FEBS Congress in St Petersburg, Russia.

机构信息

Institut Curie, Centre de Recherche, Paris, France; Centre National de la Recherche Scientifique, UMR3664, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France; Institut de Formation Doctorale, University Pierre & Marie Curie, Paris, France; Sorbonne University, PSL*, Paris, France; Epigenetics and Cell Fate Centre, UMR7216, Centre National de la Recherche Scientifique/Paris Diderot University, Paris, France.

出版信息

FEBS J. 2014 May;281(10):2315-23. doi: 10.1111/febs.12793. Epub 2014 Apr 9.

Abstract

Histone deposition onto DNA assisted by specific chaperones forms the chromatin basic unit and serves to package the genome within the cell nucleus. The resulting chromatin organization, often referred to as the epigenome, contributes to a unique transcriptional program that defines cell identity. Importantly, during cellular life, substantial alterations in chromatin structure may arise due to cell stress, including DNA damage, which not only challenges the integrity of the genome but also threatens the epigenome. Considerable efforts have been made to decipher chromatin dynamics in response to genotoxic stress, and to assess how it affects both genome and epigenome stability. Here, we review recent advances in understanding the mechanisms of DNA damage-induced chromatin plasticity in mammalian cells. We focus specifically on the dynamics of histone H3 variants in response to UV irradiation, and highlight the role of their dedicated chaperones in restoring both chromatin structure and function. Finally, we discuss how, in addition to restoring chromatin integrity, the cellular networks that signal and repair DNA damage may also provide a window of opportunity for modulating the information conveyed by chromatin.

摘要

组蛋白通过特定的伴侣蛋白沉积到 DNA 上,形成染色质的基本单位,并将基因组包装在细胞核内。由此产生的染色质组织,通常被称为表观基因组,有助于形成一个独特的转录程序,定义细胞的身份。重要的是,在细胞的生命周期中,由于细胞应激,包括 DNA 损伤,染色质结构可能会发生实质性的改变,这不仅挑战了基因组的完整性,也威胁到了表观基因组。人们已经做出了巨大的努力来解析染色质对基因毒性应激的动态变化,并评估其对基因组和表观基因组稳定性的影响。在这里,我们综述了近年来对哺乳动物细胞中 DNA 损伤诱导的染色质可塑性机制的理解的进展。我们特别关注 UV 照射下组蛋白 H3 变体的动力学,并强调其专用伴侣蛋白在恢复染色质结构和功能方面的作用。最后,我们讨论了除了恢复染色质的完整性外,信号转导和修复 DNA 损伤的细胞网络也可能为调节染色质所传递的信息提供一个机会窗口。

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