Although homologous recombination (HR) is an important pathway for DNA repair, 
it can also be a cause for deleterious genomic rearrangements leading to 
carcinogenesis. Therefore, cells have evolved elaborate mechanisms to regulate 
HR, positively as well as negatively. Among many molecular components that 
regulate HR are tumour suppressors p53, a negative regulator and breast cancer 
early-onset (BRCA)2, a positive regulator. Both the players not only interact 
with each other but also directly interact with human RAD51 (hRAD51), the key 
recombinase in HR. Here, for the first time we studied HR regulation by the 
combined action of p53 and BRCA2, in vitro. While BRC4 peptide inhibits ATP 
hydrolysis by hRAD51, BRCA2(BRC1-8) stimulates DNA-independent and 
double-stranded DNA-dependent ATPase several fold and only marginally 
single-stranded DNA-dependent ATPase. Pull down assays demonstrated the 
occurrence of complex comprising of all three proteins and DNA, where p53 tends 
to compete out hRAD51 and BRCA2(BRC1-8), leading to not only the decline in ATP 
hydrolysis but also the strand exchange function of hRAD51 that was stimulated 
by BRCA2(BRC1-8). Our findings suggest a rigorous p53-mediated regulation on 
hRAD51 functions in HR even in the presence of BRCA2.