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染色质蛋白在DNA损伤识别与修复中的作用。

The role of chromatin proteins in DNA damage recognition and repair.

作者信息

Widlak Piotr, Pietrowska Monika, Lanuszewska Joanna

机构信息

Department of Experimental and Clinical Radiobiology, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Wybrzeze AK 15, 44-100, Gliwice, Poland.

出版信息

Histochem Cell Biol. 2006 Jan;125(1-2):119-26. doi: 10.1007/s00418-005-0053-5.

Abstract

The structure of chromatin is the major factor determining the rate and efficiency of DNA repair. Chromatin remodeling events such as rearrangement of nucleosomes and higher order chromatin structures are indispensable features of repair processes. During the last decade numerous chromatin proteins have been identified that preferentially bind to different types of DNA damage. The HMGB proteins, which preferentially interact with DNA intrastrand crosslinks induced by cisplatin, are the archetypal example of such proteins. Several hypothetical models have been proposed describing the role of such damage-binding chromatin proteins. The damage shielding model postulates that binding of chromatin proteins to damaged DNA might disturb damage recognition by repair factors and impair its removal. Alternatively, the damage-recognition/signaling model proposes that the binding of specific chromatin proteins to damaged DNA could serve as a hallmark to be recognized by repair proteins. Additionally, the binding of specific chromatin proteins to damaged DNA could induce chromatin remodeling at the damage site and indirectly affect its repair. This paper aims to critically review current experimental data in relation to such possible roles of chromatin proteins.

摘要

染色质结构是决定DNA修复速率和效率的主要因素。染色质重塑事件,如核小体重排和更高层次的染色质结构,是修复过程中不可或缺的特征。在过去十年中,已鉴定出许多优先结合不同类型DNA损伤的染色质蛋白。HMGB蛋白优先与顺铂诱导的DNA链内交联相互作用,是这类蛋白的典型例子。已经提出了几个假设模型来描述这类损伤结合染色质蛋白的作用。损伤屏蔽模型假定染色质蛋白与受损DNA的结合可能会干扰修复因子对损伤的识别并损害其去除。另外,损伤识别/信号模型提出特定染色质蛋白与受损DNA的结合可以作为被修复蛋白识别的标志。此外,特定染色质蛋白与受损DNA的结合可以在损伤部位诱导染色质重塑并间接影响其修复。本文旨在批判性地综述与染色质蛋白这些可能作用相关的当前实验数据。

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