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核苷酸切除修复蛋白在清除氧化 DNA 损伤中的作用。

The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage.

机构信息

Molecular Genetics and Developmental Biology Graduate Program, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 USA.

UPMC Hillman Cancer Center, University of Pittsburgh, PA 15213, USA.

出版信息

Nucleic Acids Res. 2020 Nov 18;48(20):11227-11243. doi: 10.1093/nar/gkaa777.

Abstract

The six major mammalian DNA repair pathways were discovered as independent processes, each dedicated to remove specific types of lesions, but the past two decades have brought into focus the significant interplay between these pathways. In particular, several studies have demonstrated that certain proteins of the nucleotide excision repair (NER) and base excision repair (BER) pathways work in a cooperative manner in the removal of oxidative lesions. This review focuses on recent data showing how the NER proteins, XPA, XPC, XPG, CSA, CSB and UV-DDB, work to stimulate known glycosylases involved in the removal of certain forms of base damage resulting from oxidative processes, and also discusses how some oxidative lesions are probably directly repaired through NER. Finally, since many glycosylases are inhibited from working on damage in the context of chromatin, we detail how we believe UV-DDB may be the first responder in altering the structure of damage containing-nucleosomes, allowing access to BER enzymes.

摘要

六大主要哺乳动物 DNA 修复途径被发现为独立的过程,每个过程都专门用于去除特定类型的损伤,但在过去的二十年中,这些途径之间的显著相互作用成为了焦点。特别是,一些研究表明,核苷酸切除修复(NER)和碱基切除修复(BER)途径中的某些蛋白质以协同方式在去除氧化损伤方面发挥作用。这篇综述重点介绍了最近的数据,这些数据表明 NER 蛋白 XPA、XPC、XPG、CSA、CSB 和 UV-DDB 如何促进已知的糖苷酶参与去除氧化过程中产生的某些形式的碱基损伤,并还讨论了某些氧化损伤如何可能通过 NER 直接修复。最后,由于许多糖苷酶在染色质环境中对损伤的作用受到抑制,我们详细介绍了我们如何相信 UV-DDB 可能是第一个改变含有核小体的损伤结构的响应者,从而允许 BER 酶进入。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/614e/7672477/9d4560a6d7f2/gkaa777fig1.jpg

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