Functional characterization of BRCA1 and BRCA2: clues from their interacting proteins.

The familial breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2 have been the subject of extensive functional analysis studies since their cloning. Clues to their biological role in maintaining the genomic integrity were provided by studies that revealed their interaction with the recombination repair protein HsRad51. The first clue of an interaction between HsRad51 and BRCA1 came from the colocalization of the characteristic nuclear foci formed by these two proteins during S phase of the cell cycle. An interaction between murine Brca2 and MmRad51 was detected by the yeast two hybrid system. Utilizing the yeast two hybrid system and other techniques several other Brca1 and Brca2 interacting proteins have been identified like, BARD1, importin-alpha, BIPs, RNA polymerase II holoenzyme, BRAP2 etc. Recently, mutations suggesting a role as a tumor suppressor have been identified in the BARD1 gene in primary human tumors. The identification of molecules that interact with Brca1 and Brca2 has greatly enhanced our knowledge of how BRCA1 and BRCA2 may function as tumor suppressors.