CtIP is required to initiate replication-dependent interstrand crosslink repair.
DNA interstrand crosslinks (ICLs) are toxic lesions that block the progression of replication and transcription. CtIP is a conserved DNA repair protein that facilitates DNA end resection in the double-strand break (DSB) repair pathway. Here we show that CtIP plays a critical role during initiation o...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:8f6f239b578c43518c801b93d319f1762021-11-18T06:20:34ZCtIP is required to initiate replication-dependent interstrand crosslink repair.1553-73901553-740410.1371/journal.pgen.1003050https://doaj.org/article/8f6f239b578c43518c801b93d319f1762012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144634/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404DNA interstrand crosslinks (ICLs) are toxic lesions that block the progression of replication and transcription. CtIP is a conserved DNA repair protein that facilitates DNA end resection in the double-strand break (DSB) repair pathway. Here we show that CtIP plays a critical role during initiation of ICL processing in replicating human cells that is distinct from its role in DSB repair. CtIP depletion sensitizes human cells to ICL inducing agents and significantly impairs the accumulation of DNA damage response proteins RPA, ATR, FANCD2, γH2AX, and phosphorylated ATM at sites of laser generated ICLs. In contrast, the appearance of γH2AX and phosphorylated ATM at sites of laser generated double strand breaks (DSBs) is CtIP-independent. We present a model in which CtIP functions early in ICL repair in a BRCA1- and FANCM-dependent manner prior to generation of DSB repair intermediates.Michelle L DuquetteQingyuan ZhuEwan R TaylorAngela J TsayLinda Z ShiMichael W BernsClare H McGowanPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 8, Iss 11, p e1003050 (2012) |
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DOAJ |
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Genetics QH426-470 |
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Genetics QH426-470 Michelle L Duquette Qingyuan Zhu Ewan R Taylor Angela J Tsay Linda Z Shi Michael W Berns Clare H McGowan CtIP is required to initiate replication-dependent interstrand crosslink repair. |
description |
DNA interstrand crosslinks (ICLs) are toxic lesions that block the progression of replication and transcription. CtIP is a conserved DNA repair protein that facilitates DNA end resection in the double-strand break (DSB) repair pathway. Here we show that CtIP plays a critical role during initiation of ICL processing in replicating human cells that is distinct from its role in DSB repair. CtIP depletion sensitizes human cells to ICL inducing agents and significantly impairs the accumulation of DNA damage response proteins RPA, ATR, FANCD2, γH2AX, and phosphorylated ATM at sites of laser generated ICLs. In contrast, the appearance of γH2AX and phosphorylated ATM at sites of laser generated double strand breaks (DSBs) is CtIP-independent. We present a model in which CtIP functions early in ICL repair in a BRCA1- and FANCM-dependent manner prior to generation of DSB repair intermediates. |
format |
article |
author |
Michelle L Duquette Qingyuan Zhu Ewan R Taylor Angela J Tsay Linda Z Shi Michael W Berns Clare H McGowan |
author_facet |
Michelle L Duquette Qingyuan Zhu Ewan R Taylor Angela J Tsay Linda Z Shi Michael W Berns Clare H McGowan |
author_sort |
Michelle L Duquette |
title |
CtIP is required to initiate replication-dependent interstrand crosslink repair. |
title_short |
CtIP is required to initiate replication-dependent interstrand crosslink repair. |
title_full |
CtIP is required to initiate replication-dependent interstrand crosslink repair. |
title_fullStr |
CtIP is required to initiate replication-dependent interstrand crosslink repair. |
title_full_unstemmed |
CtIP is required to initiate replication-dependent interstrand crosslink repair. |
title_sort |
ctip is required to initiate replication-dependent interstrand crosslink repair. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/8f6f239b578c43518c801b93d319f176 |
work_keys_str_mv |
AT michellelduquette ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair AT qingyuanzhu ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair AT ewanrtaylor ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair AT angelajtsay ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair AT lindazshi ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair AT michaelwberns ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair AT clarehmcgowan ctipisrequiredtoinitiatereplicationdependentinterstrandcrosslinkrepair |
_version_ |
1718424493260537856 |