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Molecular and Cellular Biology, November 2004, p. 9478-9486, Vol. 24, No. 21
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.21.9478-9486.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal Domains

Xiaochun Yu and Junjie Chen*

Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota

Received 25 May 2004/ Returned for modification 17 June 2004/ Accepted 2 August 2004

The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho-protein binding domain. We demonstrate here that a CTBP-interacting protein CtIP interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner. The CtIP/BRCA1 complex only exists in G2 phase and is required for DNA damage-induced Chk1 phosphorylation and the G2/M transition checkpoint. However, the CtIP/BRCA1 complex is not required for the damage-induced G2 accumulation checkpoint, which is controlled by a separate BRCA1/BACH1 complex. Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage.

* Corresponding author. Mailing address: Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905. Phone: (507) 284-2511. Fax: (507) 284-3906. E-mail: chen.junjie{at}mayo.edu.

Molecular and Cellular Biology, November 2004, p. 9478-9486, Vol. 24, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.21.9478-9486.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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