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基因组稳定性中的DNA-蛋白质交联蛋白酶

DNA-protein crosslink proteases in genome stability.

作者信息

Ruggiano Annamaria, Ramadan Kristijan

机构信息

Medical Research Council (MRC) Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Roosevelt Drive, OX3 7DQ, Oxford, UK.

出版信息

Commun Biol. 2021 Jan 4;4(1):11. doi: 10.1038/s42003-020-01539-3.

DOI:10.1038/s42003-020-01539-3
PMID:33398053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7782752/
Abstract

Proteins covalently attached to DNA, also known as DNA-protein crosslinks (DPCs), are common and bulky DNA lesions that interfere with DNA replication, repair, transcription and recombination. Research in the past several years indicates that cells possess dedicated enzymes, known as DPC proteases, which digest the protein component of a DPC. Interestingly, DPC proteases also play a role in proteolysis beside DPC repair, such as in degrading excess histones during DNA replication or controlling DNA replication checkpoints. Here, we discuss the importance of DPC proteases in DNA replication, genome stability and their direct link to human diseases and cancer therapy.

摘要

与DNA共价连接的蛋白质,也被称为DNA-蛋白质交联物(DPCs),是常见且体积较大的DNA损伤,会干扰DNA复制、修复、转录和重组。过去几年的研究表明,细胞拥有专门的酶,即DPC蛋白酶,可消化DPC的蛋白质成分。有趣的是,DPC蛋白酶除了在DPC修复中发挥作用外,在蛋白水解过程中也发挥作用,比如在DNA复制过程中降解多余的组蛋白或控制DNA复制检查点。在此,我们讨论DPC蛋白酶在DNA复制、基因组稳定性中的重要性,以及它们与人类疾病和癌症治疗的直接联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/f12293300b49/42003_2020_1539_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/578a14f2abaf/42003_2020_1539_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/b538d7f3156e/42003_2020_1539_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/566c5e75d7a6/42003_2020_1539_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/f12293300b49/42003_2020_1539_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/578a14f2abaf/42003_2020_1539_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/b538d7f3156e/42003_2020_1539_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/566c5e75d7a6/42003_2020_1539_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac5a/7782752/f12293300b49/42003_2020_1539_Fig4_HTML.jpg

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Cell Rep. 2021 Dec 7;37(10):110080. doi: 10.1016/j.celrep.2021.110080.
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Nucleic Acids Res. 2025 Feb 8;53(4). doi: 10.1093/nar/gkaf061.
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Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.瓣内切核酸酶1通过依赖于ADP-核糖基化的机制修复DNA-蛋白质交联。
Sci Adv. 2025 Jan 10;11(2):eads2919. doi: 10.1126/sciadv.ads2919.
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Homozygous synonymous FAM111A variant underlies an autosomal recessive form of Kenny-Caffey syndrome.纯合同义FAM111A变异是肯尼-卡菲综合征常染色体隐性形式的基础。
J Hum Genet. 2025 Feb;70(2):87-97. doi: 10.1038/s10038-024-01301-1. Epub 2024 Nov 6.
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