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CtIP is required to initiate replication-dependent interstrand crosslink repair.

ABSTRACT: 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, ?H2AX, and phosphorylated ATM at sites of laser generated ICLs. In contrast, the appearance of ?H2AX 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.

SUBMITTER: Duquette ML

PROVIDER: S-EPMC3493458 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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CtIP is required to initiate replication-dependent interstrand crosslink repair.

Duquette Michelle L ML Zhu Qingyuan Q Taylor Ewan R ER Tsay Angela J AJ Shi Linda Z LZ Berns Michael W MW McGowan Clare H CH

PLoS genetics 20121108 11

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 ...[more]

PMID: 23144634

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