The RAD51 gene family, genetic instability and cancer

Inefficient repair or mis-repair of DNA damage can cause genetic instability, and defects in some DNA repair genes are associated with rare human cancer-prone disorders. In the last few years, homologous recombination has been found to be a key pathway in human cells for the repair of severe DNA damage such as double-strand breaks. The RAD51 family of genes, including RAD51 and the five RAD51-like genes (XRCC2, XRCC3, RAD51L1, RAD51L2, RAD51L3) are known to have crucial non-redundant roles in this pathway. Current knowledge of the functions of the RAD51 gene family is reviewed, as well as the evidence for extensive genetic instability arising from loss of their activity. Reports of potential associations between variants of RAD51 family genes and specific forms of cancer are summarized, but it is seen that many of these studies have relatively low statistical power. As yet these data provide only tantalizing suggestions of modified cancer risks arising from polymorphisms, mutations, or changes in expression of the RAD51 gene family, and there is still a lot to learn before firm conclusions can be made.