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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Autores principales: Michelle L Duquette, Qingyuan Zhu, Ewan R Taylor, Angela J Tsay, Linda Z Shi, Michael W Berns, Clare H McGowan
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/8f6f239b578c43518c801b93d319f176
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Genetics
QH426-470
spellingShingle 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
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