DNA-binding and strand-annealing activities of human Mre11: implications for its roles in DNA double-strand break repair pathways

DNA double-strand breaks (DSBs) in eukaryotic cells can be repaired by non- homologous end-joining or homologous recombination. The complex containing the Mre11, Rad50 and Nbs1 proteins has been implicated in both DSB repair p athways, even though they are mechanistically different. To get a better un derstanding of the properties of the human Mre11 (hMre11) protein, we inves tigated some of its biochemical activities. We found that hMre11 binds both double- and single-stranded (ss)DNA, with a preference for ssDNA, hMre11 d oes not require DNA ends for efficient binding. Interestingly, hMre11 media tes the annealing of complementary ssDNA molecules, In contrast to the anne aling activity of the homologous recombination protein hRad52, the activity of hMre11 is abrogated by the ssDNA binding protein hRPA, We discuss the p ossible implications of the results for the role(s) of hMre11 in both DSB r epair pathways.