A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression

Germline mutations of the human BRCA2 gene confer susceptibility to breast cancer. Although the function of the BRCA2 protein remains to be determined , murine cells homozygous for BRCA2 inactivation display chromosomal aberra tions. We have isolated a 2 MDa BRCA2-containing complex and identified a s tructural DNA binding component, designated as BRCA2-Associated Factor 35 ( BRAF35). BRAF35 contains a nonspecific DNA binding HMG domain and a kinesin -like coiled coil domain. Similar to BRCA2, BRAF35 mRNA expression levels i n mouse embryos are highest in proliferating tissues with high mitotic inde x. Strikingly, nuclear staining revealed a close association of BRAF35/BRCA 2 complex with condensed chromatin coincident with histone H3 phosphorylati on. Importantly, antibody microinjection experiments suggest a role for BRC A2/BRAF35 complex in modulation of cell cycle progression.