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

Cdk1 使 CtIP 依赖性的切除和 Rad51 丝形成在 M 期双链断裂修复过程中解偶联。

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

机构信息

Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.

出版信息

J Cell Biol. 2011 Sep 5;194(5):705-20. doi: 10.1083/jcb.201103103.

DOI:10.1083/jcb.201103103
PMID:21893598
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3171114/
Abstract

DNA double-strand break (DSB) resection, which results in RPA-bound single-stranded DNA (ssDNA), is activated in S phase by Cdk2. RPA-ssDNA activates the ATR-dependent checkpoint and homology-directed repair (HDR) via Rad51-dependent mechanisms. On the other hand, the fate of DSBs sustained during vertebrate M phase is largely unknown. We use cell-free Xenopus laevis egg extracts to examine the recruitment of proteins to chromatin after DSB formation. We find that S-phase extract recapitulates a two-step resection mechanism. M-phase chromosomes are also resected in cell-free extracts and cultured human cells. In contrast to the events in S phase, M-phase resection is solely dependent on MRN-CtIP. Despite generation of RPA-ssDNA, M-phase resection does not lead to ATR activation or Rad51 chromatin association. Remarkably, we find that Cdk1 permits resection by phosphorylation of CtIP but also prevents Rad51 binding to the resected ends. We have thus identified Cdk1 as a critical regulator of DSB repair in M phase. Cdk1 induces persistent ssDNA-RPA overhangs in M phase, thereby preventing both classical NHEJ and Rad51-dependent HDR.

摘要

DNA 双链断裂 (DSB) 的切除，导致 RPA 结合的单链 DNA (ssDNA)，在 S 期被 Cdk2 激活。RPA-ssDNA 通过 Rad51 依赖性机制激活 ATR 依赖性检查点和同源定向修复 (HDR)。另一方面，脊椎动物 M 期持续存在的 DSBs 的命运在很大程度上是未知的。我们使用无细胞非洲爪蟾卵提取物来研究 DSB 形成后蛋白质在染色质上的募集。我们发现 S 期提取物再现了两步切除机制。无细胞提取物和培养的人类细胞也能切除 M 期染色体。与 S 期的事件相反，M 期的切除仅依赖于 MRN-CtIP。尽管产生了 RPA-ssDNA，但 M 期的切除不会导致 ATR 的激活或 Rad51 与染色质的结合。值得注意的是，我们发现 Cdk1 通过磷酸化 CtIP 来允许切除，但也阻止 Rad51 结合到切除的末端。因此，我们将 Cdk1 鉴定为 M 期 DSB 修复的关键调节剂。Cdk1 在 M 期诱导持续的 ssDNA-RPA 突出，从而防止经典的 NHEJ 和 Rad51 依赖性 HDR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/acebdbb76d22/JCB_201103103_RGB_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/f54f4a63128b/JCB_201103103_GS_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/d2920085f398/JCB_201103103_GS_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/581a01d4d3d9/JCB_201103103_GS_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/384965449538/JCB_201103103_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/ae191f32acff/JCB_201103103_GS_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/757abdbdbbb5/JCB_201103103_GS_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/acebdbb76d22/JCB_201103103_RGB_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/f54f4a63128b/JCB_201103103_GS_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/d2920085f398/JCB_201103103_GS_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/581a01d4d3d9/JCB_201103103_GS_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/384965449538/JCB_201103103_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/ae191f32acff/JCB_201103103_GS_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/757abdbdbbb5/JCB_201103103_GS_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e9b/3171114/acebdbb76d22/JCB_201103103_RGB_Fig7.jpg

相似文献

[1]
Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M-phase double-strand break repair.

J Cell Biol. 2011-9-5

[2]
Xenopus DNA2 is a helicase/nuclease that is found in complexes with replication proteins And-1/Ctf4 and Mcm10 and DSB response proteins Nbs1 and ATM.

Cell Cycle. 2010-3-15

[3]
Activation of DSB processing requires phosphorylation of CtIP by ATR.

Mol Cell. 2012-12-27

[4]
RPA accumulation during class switch recombination represents 5'-3' DNA-end resection during the S-G2/M phase of the cell cycle.

Cell Rep. 2013-1-3

[5]
Dna2 initiates resection at clean DNA double-strand breaks.

Nucleic Acids Res. 2017-11-16

[6]
Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.

PLoS Genet. 2011-9-8

[7]
The MRE11 GAR motif regulates DNA double-strand break processing and ATR activation.

Cell Res. 2011-8-9

[8]
Replication protein A promotes 5'-->3' end processing during homology-dependent DNA double-strand break repair.

J Cell Biol. 2011-1-24

[9]
CtIP interacts with TopBP1 and Nbs1 in the response to double-stranded DNA breaks (DSBs) in Xenopus egg extracts.

Cell Cycle. 2011-2-1

[10]
DNA end resection is needed for the repair of complex lesions in G1-phase human cells.

Cell Cycle. 2014

引用本文的文献

[1]
DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.

Nat Commun. 2025-8-25

[2]
Mechanisms and regulation of DNA end resection in the maintenance of genome stability.

Nat Rev Mol Cell Biol. 2025-3-25

[3]
CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes.

BMC Biol. 2025-2-6

[4]
A TRilogy of ATR's Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer.

Cancers (Basel). 2024-10-19

[5]
53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).

Nat Commun. 2024-10-5

[6]
53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).

bioRxiv. 2024-9-13

[7]
Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination.

Nat Commun. 2024-4-3

[8]
Modulation of cell cycle increases CRISPR-mediated homology-directed DNA repair.

Cell Biosci. 2023-11-25

[9]
CRISPR/Cas9 system and its applications in nervous system diseases.

Genes Dis. 2023-4-13

[10]
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis.

Nature. 2023-9

本文引用的文献

[1]
Give me a break, but not in mitosis: the mitotic DNA damage response marks DNA double-strand breaks with early signaling events.

Cell Cycle. 2011-4-15

[2]
BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair.

Genes Dev. 2011-2-15

[3]
53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress.

Nat Cell Biol. 2011-2-13

[4]
CtIP promotes microhomology-mediated alternative end joining during class-switch recombination.

Nat Struct Mol Biol. 2010-12-5

[5]
An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway.

Nat Struct Mol Biol. 2010-12-5

[6]
Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks.

EMBO J. 2010-9-10

[7]
DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11-Rad50-Xrs2.

Nature. 2010-9-2

[8]
Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae.

Nature. 2010-9-2

[9]
The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers.

Adv Immunol. 2010

[10]
DNA damage signaling in response to double-strand breaks during mitosis.

J Cell Biol. 2010-7-26

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