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

人类CtIP蛋白促进DNA末端切除。

Human CtIP promotes DNA end resection.

作者信息

Sartori Alessandro A, Lukas Claudia, Coates Julia, Mistrik Martin, Fu Shuang, Bartek Jiri, Baer Richard, Lukas Jiri, Jackson Stephen P

机构信息

The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

出版信息

Nature. 2007 Nov 22;450(7169):509-14. doi: 10.1038/nature06337. Epub 2007 Oct 28.

DOI:10.1038/nature06337
PMID:17965729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2409435/
Abstract

In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.

摘要

在细胞周期的S期和G2期，DNA双链断裂（DSB）被加工成单链DNA，触发依赖ATR的检查点信号传导以及通过同源重组进行的DSB修复。先前的研究表明MRE11复合物参与此类DSB加工事件。在此，我们表明人类CtIP（RBBP8）蛋白赋予细胞对DSB诱导剂的抗性，并且仅在S期和G2期细胞周期阶段被招募到DSB处。此外，我们发现CtIP是DSB切除所必需的，因此也是复制蛋白A（RPA）和蛋白激酶ATR招募到DSB处以及随后的ATR激活所必需的。此外，我们证实CtIP在物理和功能上与MRE11复合物相互作用，并且CtIP和MRE11都是高效同源重组所必需的。最后，我们发现CtIP与Sae2具有序列同源性，Sae2参与酵母中依赖MRE11的DSB加工。这些发现确立了CtIP样蛋白在控制DSB切除、检查点信号传导和同源重组方面的进化保守作用。

相似文献

[1]
Human CtIP promotes DNA end resection.

Nature. 2007-11-22

[2]
CtIP/Ctp1/Sae2, molecular form fit for function.

DNA Repair (Amst). 2017-8

[3]
CtIP links DNA double-strand break sensing to resection.

Mol Cell. 2009-12-25

[4]
Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair.

J Biol Chem. 2008-3-21

[5]
N terminus of CtIP is critical for homologous recombination-mediated double-strand break repair.

J Biol Chem. 2009-11-13

[6]
Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M-phase double-strand break repair.

J Cell Biol. 2011-9-5

[7]
DNA end resection is needed for the repair of complex lesions in G1-phase human cells.

Cell Cycle. 2014

[8]
CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle.

Nature. 2009-5-21

[9]
Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks.

Mol Cell. 2009-3-13

[10]
BRCA1 and CtIP Are Both Required to Recruit Dna2 at Double-Strand Breaks in Homologous Recombination.

PLoS One. 2015-4-24

引用本文的文献

[1]
Phase separation of ERCC6L2-CtIP regulates the extent of DNA end resection.

Nat Cell Biol. 2025-9-5

[2]
DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.

Nat Commun. 2025-8-25

[3]
XPO1R749Q Mutations Co-occur with POLE Mutations in Cancer and can be Targeted to Overcome Chemoresistance.

Cancer Res. 2025-6-18

[4]
ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome.

Nat Cell Biol. 2025-6

[5]
Inherited deficiency of DIAPH1 identifies a DNA double strand break repair pathway regulated by γ-actin.

Nat Commun. 2025-5-14

[6]
Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection.

Nat Commun. 2025-4-16

[7]
The PIN1-p38-CtIP signalling axis protects stalled replication forks from deleterious degradation.

Nucleic Acids Res. 2025-4-10

[8]
Proteomic Sensors for Quantitative, Multiplexed and Spatial Monitoring of Kinase Signaling.

Res Sq. 2025-3-27

[9]
Mechanisms and regulation of DNA end resection in the maintenance of genome stability.

Nat Rev Mol Cell Biol. 2025-3-25

[10]
Effect of Brief Maternal Exposure to Bisphenol A on the Fetal Female Germline in a Mouse Model.

Environ Health Perspect. 2025-4

本文引用的文献

[1]
Mechanism of homologous recombination: mediators and helicases take on regulatory functions.

Nat Rev Mol Cell Biol. 2006-10

[2]
DNA double-strand break repair: all's well that ends well.

Annu Rev Genet. 2006

[3]
CtIP, a multivalent adaptor connecting transcriptional regulation, checkpoint control and tumor suppression.

Cell Cycle. 2006-8

[4]
Budding Yeast Sae2 is an In Vivo Target of the Mec1 and Tel1 Checkpoint Kinases During Meiosis.

Cell Cycle. 2006-7

[5]
BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.

Genes Dev. 2006-7-1

[6]
Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks.

J Cell Biol. 2006-4-24

[7]
Differential involvement of phosphatidylinositol 3-kinase-related protein kinases in hyperphosphorylation of replication protein A2 in response to replication-mediated DNA double-strand breaks.

Genes Cells. 2006-3

[8]
Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex.

Oncogene. 2006-6-29

[9]
ATM regulates ATR chromatin loading in response to DNA double-strand breaks.

J Exp Med. 2006-2-20

[10]
Rapid activation of ATR by ionizing radiation requires ATM and Mre11.

J Biol Chem. 2006-4-7

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