文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

PARP/NAD/SIRT6 轴调控碱基切除/单链断裂修复蛋白复合物的组装/解组装的时动态变化。

Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD/SIRT6 axis.

机构信息

Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA; Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36604, USA.

Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.

出版信息

Cell Rep. 2021 Nov 2;37(5):109917. doi: 10.1016/j.celrep.2021.109917.

DOI:10.1016/j.celrep.2021.109917
PMID:34731617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8607749/
Abstract

Assembly and disassembly of DNA repair protein complexes at DNA damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly of the base excision repair (BER) proteins DNA polymerase β (Polβ) and XRCC1 to DNA lesion sites identifies a role for Polβ in regulating XRCC1 disassembly from DNA repair complexes and, conversely, demonstrates Polβ's dependence on XRCC1 for complex assembly. LivePAR, a genetically encoded probe for live-cell imaging of poly(ADP-ribose) (PAR), reveals that Polβ and XRCC1 require PAR for repair-complex assembly, with PARP1 and PARP2 playing unique roles in complex dynamics. Further, BER complex assembly is modulated by attenuation/augmentation of NAD biosynthesis. Finally, SIRT6 does not modulate PARP1 or PARP2 activation but does regulate XRCC1 recruitment, leading to diminished Polβ abundance at sites of DNA damage. These findings highlight coordinated yet independent roles for PARP1, PARP2, and SIRT6 and their regulation by NAD bioavailability to facilitate BER.

摘要

DNA 修复蛋白复合物在 DNA 损伤部位的组装和拆卸对于维持基因组完整性至关重要。研究协调碱基切除修复 (BER) 蛋白 DNA 聚合酶 β (Polβ) 和 XRCC1 组装到 DNA 损伤部位的因素，鉴定了 Polβ 在调节 XRCC1 从 DNA 修复复合物中拆卸的作用，反之，也证明了 Polβ 对 XRCC1 组装复合物的依赖性。LivePAR 是一种用于活细胞多聚 ADP-核糖 (PAR) 成像的基因编码探针，表明 Polβ 和 XRCC1 需要 PAR 才能组装修复复合物，而 PARP1 和 PARP2 在复合物动力学中发挥独特作用。此外，BER 复合物的组装受到 NAD 生物合成的衰减/增强的调节。最后，SIRT6 不会调节 PARP1 或 PARP2 的激活，但会调节 XRCC1 的募集，导致 DNA 损伤部位的 Polβ 丰度降低。这些发现强调了 PARP1、PARP2 和 SIRT6 的协调但独立的作用，以及 NAD 生物利用度对其调节以促进 BER。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/47bebd555e0b/nihms-1753632-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/03775cc43d07/nihms-1753632-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/4aee184072c7/nihms-1753632-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/88955309c6d0/nihms-1753632-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/ec0fc18b38be/nihms-1753632-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/e70ae64710bb/nihms-1753632-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/47617065ba57/nihms-1753632-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/47bebd555e0b/nihms-1753632-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/03775cc43d07/nihms-1753632-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/4aee184072c7/nihms-1753632-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/88955309c6d0/nihms-1753632-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/ec0fc18b38be/nihms-1753632-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/e70ae64710bb/nihms-1753632-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/47617065ba57/nihms-1753632-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7e/8607749/47bebd555e0b/nihms-1753632-f0008.jpg

相似文献

[1]
Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD/SIRT6 axis.

Cell Rep. 2021-11-2

[2]
XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites.

Nucleic Acids Res. 2025-2-8

[3]
Oncometabolite 2-hydroxyglutarate suppresses basal protein levels of DNA polymerase beta that enhances alkylating agent and PARG inhibition induced cytotoxicity.

DNA Repair (Amst). 2024-8

[4]
Quantitative Analysis of Nuclear Poly(ADP-Ribose) Dynamics in Response to Laser-Induced DNA Damage.

Methods Mol Biol. 2023

[5]
NAD-mediated regulation of mammalian base excision repair.

DNA Repair (Amst). 2020-9

[6]
Functional Roles of PARP2 in Assembling Protein-Protein Complexes Involved in Base Excision DNA Repair.

Int J Mol Sci. 2021-4-28

[7]
[Influence of the Poly(ADP-Ribose) Polymerase 1 Level on the Status of Base Excision Repair in Human Cells].

Mol Biol (Mosk). 2023

[8]
XRCC1 prevents toxic PARP1 trapping during DNA base excision repair.

Mol Cell. 2021-7-15

[9]
Polβ/XRCC1 heterodimerization dictates DNA damage recognition and basal Polβ protein levels without interfering with mouse viability or fertility.

DNA Repair (Amst). 2023-3

[10]
The dynamics and regulation of PARP1 and PARP2 in response to DNA damage and during replication.

DNA Repair (Amst). 2024-8

引用本文的文献

[1]
PARP (Poly ADP-ribose Polymerase) Family in Health and Disease.

MedComm (2020). 2025-9-1

[2]
TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair.

Nucleic Acids Res. 2025-6-20

[3]
Exposure of cells to near-infrared irradiation relaxes chromatin compaction and facilitates recognition of cyclo-butane pyrimidine dimers.

Sci Rep. 2025-7-1

[4]
DNA polymerase beta expression in head & neck cancer modulates the poly(ADP-ribose)-mediated replication checkpoint.

DNA Repair (Amst). 2025-6

[5]
Development and characterization of a novel NEIL1 nanobody.

DNA Repair (Amst). 2025-6

[6]
Overexpression of the WWE domain of RNF146 modulates poly-(ADP)-ribose dynamics at sites of DNA damage.

DNA Repair (Amst). 2025-6

[7]
Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.

Biomolecules. 2024-12-6

[8]
PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.

EMBO Rep. 2024-12

[9]
Divalent and multivalent cations control liquid-like assembly of poly(ADP-ribosyl)ated PARP1 into multimolecular associates in vitro.

Commun Biol. 2024-9-15

[10]
Poly-ADP-ribosylation dynamics, signaling, and analysis.

Environ Mol Mutagen. 2024-11

本文引用的文献

[1]
The therapeutic promises of NAD boosters.

Cell Metab. 2021-7-6

[2]
UniProt: the universal protein knowledgebase in 2021.

Nucleic Acids Res. 2021-1-8

[3]
Dihydronicotinamide riboside promotes cell-specific cytotoxicity by tipping the balance between metabolic regulation and oxidative stress.

PLoS One. 2020

[4]
NAD-mediated regulation of mammalian base excision repair.

DNA Repair (Amst). 2020-9

[5]
NRH salvage and conversion to NAD requires NRH kinase activity by adenosine kinase.

Nat Metab. 2020-4

[6]
Extracellular NAD enhances PARP-dependent DNA repair capacity independently of CD73 activity.

Sci Rep. 2020-1-20

[7]
A reduced form of nicotinamide riboside defines a new path for NAD biosynthesis and acts as an orally bioavailable NAD precursor.

Mol Metab. 2019-10-3

[8]
Stability and sub-cellular localization of DNA polymerase β is regulated by interactions with NQO1 and XRCC1 in response to oxidative stress.

Nucleic Acids Res. 2019-7-9

[9]
SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species.

Cell. 2019-4-18

[10]
Dihydronicotinamide riboside is a potent NAD concentration enhancer and .

J Biol Chem. 2019-4-4

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索