The role of homologous recombination proteins in vertebrate DNA replication

Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Lesions and discontinuities in the DNA template undergoing replication induce replication fork stalling. Homologous recombination (HR) proteins RAD51 and BRCA1/2 play a major role in the stability of replication forks. This function appears to be distinct from the classical one performed by these proteins in HR dependent DNA Double Strand Break repair. Using Xenopus laevis egg extract we discovered that RAD51 prevents MRE11 mediated degradation of nascent DNA at stalled forks in eukaryotic cells. This finding has been widely confirmed in different model systems. The use of electron microscopy mediated analysis of replication intermediates is allowing the dissection of several mechanistic aspects of HR proteins function in replication fork protection. I will address the crosstalk between BRCA1/2, RAD51 and the MRE11 complex in light of our more recent findings.