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PARP1-DNA 共凝聚:断裂 DNA 修复的驱动力。

PARP1-DNA co-condensation: the driver of broken DNA repair.

机构信息

Life Sciences Institute, The Second Affiliated Hospital of the Zhejiang University School of Medicine, The MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Zhejiang University, Hangzhou, China.

The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215123, China.

出版信息

Signal Transduct Target Ther. 2024 May 17;9(1):135. doi: 10.1038/s41392-024-01832-1.

DOI:10.1038/s41392-024-01832-1
PMID:38760366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11101638/
Abstract

DNA double-strand break (DSB) sites that prevent the disjunction of broken DNA ends are formed through poly (ADP-ribose) (PAR) polymerase 1 (PARP1)-DNA co-condensation. The co-condensates apply mechanical forces to hold the DNA ends together and generate enzymatic activity for the synthesis of PAR. PARylation can promote the release of PARP1 from DNA ends and recruit various proteins, such as Fused in sarcoma (FUS) proteins, thereby stabilizing broken DNA ends and preventing their separation.

摘要

DNA 双链断裂 (DSB) 位点通过聚 (ADP-核糖) (PAR) 聚合酶 1 (PARP1)-DNA 共凝聚形成,这些位点可防止断裂 DNA 末端的分离。共凝聚物施加机械力将 DNA 末端保持在一起,并产生用于合成 PAR 的酶活性。PAR 化可以促进 PARP1 从 DNA 末端释放,并招募各种蛋白质,如肉瘤融合 (FUS) 蛋白,从而稳定断裂的 DNA 末端并防止它们分离。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3f/11101638/0e606553de3e/41392_2024_1832_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3f/11101638/5328456c20fb/41392_2024_1832_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3f/11101638/0e606553de3e/41392_2024_1832_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3f/11101638/5328456c20fb/41392_2024_1832_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a3f/11101638/0e606553de3e/41392_2024_1832_Fig1_HTML.jpg

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Cell. 2024 Feb 15;187(4):945-961.e18. doi: 10.1016/j.cell.2024.01.015. Epub 2024 Feb 5.
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PARP inhibitors: Synthetic lethality in the clinic.聚(ADP-核糖)聚合酶抑制剂:临床中的合成致死性
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A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
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Cell Genom. 2025 Jun 11;5(6):100851. doi: 10.1016/j.xgen.2025.100851. Epub 2025 Apr 17.
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Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.与神经退行性疾病相关的蛋白质:与DNA修复的联系
Biomedicines. 2024 Dec 11;12(12):2808. doi: 10.3390/biomedicines12122808.
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Oxidative DNA Damage and Arterial Hypertension in Light of Current ESC Guidelines.基于欧洲心脏病学会(ESC)现行指南探讨氧化DNA损伤与动脉高血压
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