The BRCA2 activation domain associates with and is phosphorylated by a cellular protein kinase

A substantial proportion of familiar breast cancers have mutations within t he BRCA2 gene. The product of this gene has been implicated in DNA repair a nd in the regulation of transcription. We have previously identified at the amino-terminus of BRCA2 a transcriptional activation domain whose importan ce is highlighted by the presence of predisposing mutations and in-frame de letions in breast cancer families. This activation domain shows sequence si milarity to a region of c-Jun which has been defined as a binding site for the c-Jun N-terminal kinase, Here, we show that the analogous region in BRC A2 is also a binding site for a cellular kinase, although this kinase is di stinct from JNK, The BRCA2 associated enzyme Is able to phosphorylate resid ues within the BRCA2 activation domain. Consistent with this observation, w e find that the activation domain of BRCA2 is phosphorylated in vivo. Our r esults indicate that the BRCA2 activation domain possesses a binding site f or a kinase that may regulate BRCA2 activity by phosphorylation.