Int J Biol Sci 2008; 4(6):352-361. doi:10.7150/ijbs.4.352
A PP1-binding motif present in BRCA1 plays a role in its DNA repair function
1. Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, PA15213, USA
Protein phosphatase 1α (PP1α) regulates phosphorylation of BRCA1, which contains a PP1-binding motif 898KVTF901. Mutation of this motif greatly reduces the interaction between BRCA1 and PP1α. Here we show that mutation of the PP1-binding motif abolishes the ability of BRCA1 to enhance survival of Brca1-deficient mouse mammary tumor cells after DNA damage. The Rad51 focus formation and comet assays revealed that the DNA repair function of BRCA1 was impaired when the PP1-binding motif was mutated. Analysis of subnuclear localization of GFP-tagged BRCA1 demonstrated that mutation of the PP1-binding motif affected BRCA1 redistribution in response to DNA damage. BRCA1 is required for the formation of Rad51 subnuclear foci after DNA damage. Mutation of the PP1-binding motif in BRCA1 also affected recruitment of Rad51 to sites of DNA damage. Consistent with these findings, knockdown of PP1α in BRCA1-proficient cells by small interfering RNA also significantly reduced Rad51 focus formation induced by DNA damage. Further analysis indicated that mutation of the PP1-binding motif compromised BRCA1 activities in homologous recombination. Altogether, our data implicate that interaction with PP1α is important for BRCA1 function in DNA repair.
Keywords: BRCA1, protein phosphatase 1, DNA repair
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How to cite this article:
Yu YM, Pace SM, Allen SR, Deng CX, Hsu LC. A PP1-binding motif present in BRCA1 plays a role in its DNA repair function. Int J Biol Sci 2008; 4(6):352-361. doi:10.7150/ijbs.4.352. Available from http://www.ijbs.com/v04p0352.htm