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Abstract:
The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene1 (BRCA1) protein is an evolutionarily conserved module thatexists in a large number of proteins from prokaryotes to eukaryotes.Although most BRCT domaincontaining proteins participatein DNA-damage checkpoint or DNA-repair pathways, or both, thefunction of the BRCT domain is not fully understood. We showthat the BRCA1 BRCT domain directly interacts with phosphorylatedBRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specificinteraction between BRCA1 and phosphorylated BACH1 is cell cycleregulated and is required for DNA damageinduced checkpointcontrol during the transition from G2 to M phase of the cellcycle. Further, we show that two other BRCT domains interactwith their respective physiological partners in a phosphorylation-dependentmanner. Thirteen additional BRCT domains also preferentiallybind phospho-peptides rather than nonphosphorylated controlpeptides. These data imply that the BRCT domain is a phospho-proteinbinding domain involved in cell cycle control.
1 Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. 2 Department of Medical Genetics, Mayo Clinic and Foundation, Rochester, MN 55905, USA. 3 Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
* To whom correspondence should be addressed. E-mail: chen.junjie{at}mayo.edu
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