Figure 2

Network of breast cancer susceptibility proteins in DNA damage signalling and repair. Functional interplay between several known or candidate breast cancer susceptibility gene products in the intracellular response to either DNA double strand breaks (left side) or interstrand crosslinks (right side). Sensed by the Mre11-RAD50-NBN complex or by the Fanconi anemia core proteins, the respective signalling pathways merge into cell cycle arrest/apoptosis as mediated through p53, and into homology-directed recombinational repair mediated by BRCA1, PALB2, BRCA2, and the RAD51 paralogs. As mentioned in the text and in Table 1, some of the underlying genes are evidenced but have not yet been finally confirmed as bona fide breast cancer susceptibility genes, and some may mainly constitute ovarian cancer susceptibility genes. The genes for MERIT40, MDM4, and RAD51B harbour common polymorphisms associated with breast cancer, and RAD51 harbours a common SNP associated with breast cancer risk in BRCA2 mutation carriers.