hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response

Abstract

Mutations in the BRCA1 (ref. 1) tumour suppressor gene are found in almost all of the families with inherited breast and ovarian cancers and about half of the families with only breast cancer^2,3. Although the biochemical function of BRCA1 is not well understood, it is important for DNA damage repair^4,5,6,7 and cell-cycle checkpoint^8,9,10. BRCA1 exists in nuclear foci but is hyperphosphorylated and disperses after DNA damage^11,12. It is not known whether BRCA1 phosphorylation and dispersion and its function in DNA damage response are related. In yeast the DNA damage response and the replication-block checkpoint are mediated partly through the Cds1 kinase family^{13,14,15,16,17,18,19,20}. Here we report that the human Cds1 kinase (hCds1/Chk2)^{21,22,<a id="ref-link-abstract-23" title="Brown, A. L. et...}