The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair.
CtIP plays an important role in homologous recombination (HR)-mediated DNA double-stranded break (DSB) repair and interacts with Nbs1 and BRCA1, which are linked to Nijmegen breakage syndrome (NBS) and familial breast cancer, respectively. We identified new CDK phosphorylation sites on CtIP and foun...
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2013
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oai:doaj.org-article:8606f4a68b27439399514e14dd129d542021-11-18T06:20:03ZThe interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair.1553-73901553-740410.1371/journal.pgen.1003277https://doaj.org/article/8606f4a68b27439399514e14dd129d542013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23468639/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404CtIP plays an important role in homologous recombination (HR)-mediated DNA double-stranded break (DSB) repair and interacts with Nbs1 and BRCA1, which are linked to Nijmegen breakage syndrome (NBS) and familial breast cancer, respectively. We identified new CDK phosphorylation sites on CtIP and found that phosphorylation of these newly identified CDK sites induces association of CtIP with the N-terminus FHA and BRCT domains of Nbs1. We further showed that these CDK-dependent phosphorylation events are a prerequisite for ATM to phosphorylate CtIP upon DNA damage, which is important for end resection to activate HR by promoting recruitment of BLM and Exo1 to DSBs. Most notably, this CDK-dependent CtIP and Nbs1 interaction facilitates ATM to phosphorylate CtIP in a substrate-specific manner. These studies reveal one important mechanism to regulate cell-cycle-dependent activation of HR upon DNA damage by coupling CDK- and ATM-mediated phosphorylation of CtIP through modulating the interaction of CtIP with Nbs1, which significantly helps to understand how DSB repair is regulated in mammalian cells to maintain genome stability.Hailong WangLinda Z ShiCatherine C L WongXuemei HanPatty Yi-Hwa HwangLan N TruongQingyuan ZhuZhengping ShaoDavid J ChenMichael W BernsJohn R YatesLongchuan ChenXiaohua WuPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 2, p e1003277 (2013) |
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DOAJ |
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| language |
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| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Hailong Wang Linda Z Shi Catherine C L Wong Xuemei Han Patty Yi-Hwa Hwang Lan N Truong Qingyuan Zhu Zhengping Shao David J Chen Michael W Berns John R Yates Longchuan Chen Xiaohua Wu The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. |
| description |
CtIP plays an important role in homologous recombination (HR)-mediated DNA double-stranded break (DSB) repair and interacts with Nbs1 and BRCA1, which are linked to Nijmegen breakage syndrome (NBS) and familial breast cancer, respectively. We identified new CDK phosphorylation sites on CtIP and found that phosphorylation of these newly identified CDK sites induces association of CtIP with the N-terminus FHA and BRCT domains of Nbs1. We further showed that these CDK-dependent phosphorylation events are a prerequisite for ATM to phosphorylate CtIP upon DNA damage, which is important for end resection to activate HR by promoting recruitment of BLM and Exo1 to DSBs. Most notably, this CDK-dependent CtIP and Nbs1 interaction facilitates ATM to phosphorylate CtIP in a substrate-specific manner. These studies reveal one important mechanism to regulate cell-cycle-dependent activation of HR upon DNA damage by coupling CDK- and ATM-mediated phosphorylation of CtIP through modulating the interaction of CtIP with Nbs1, which significantly helps to understand how DSB repair is regulated in mammalian cells to maintain genome stability. |
| format |
article |
| author |
Hailong Wang Linda Z Shi Catherine C L Wong Xuemei Han Patty Yi-Hwa Hwang Lan N Truong Qingyuan Zhu Zhengping Shao David J Chen Michael W Berns John R Yates Longchuan Chen Xiaohua Wu |
| author_facet |
Hailong Wang Linda Z Shi Catherine C L Wong Xuemei Han Patty Yi-Hwa Hwang Lan N Truong Qingyuan Zhu Zhengping Shao David J Chen Michael W Berns John R Yates Longchuan Chen Xiaohua Wu |
| author_sort |
Hailong Wang |
| title |
The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. |
| title_short |
The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. |
| title_full |
The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. |
| title_fullStr |
The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. |
| title_full_unstemmed |
The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double-strand break repair. |
| title_sort |
interaction of ctip and nbs1 connects cdk and atm to regulate hr-mediated double-strand break repair. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/8606f4a68b27439399514e14dd129d54 |
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