RAD51 paralogs interact with the replicative helicase to bypass DNA damage

Using evolutionary approaches, we find that the yeast and human Shu complexes are co-evolving with specific replication initiation factors including the origin recognition (ORC) complex and the replicativehelicase, the minichromosome maintenance (MCM) complex. Suggesting that the yeast Shu complex physically interacts with the replication machinery, we find that multiple Shu complex members interact with the ORC and MCM complexes by yeast-2-hybrid and co-immunoprecipitation experiments. We propose that the Shu complex is loaded onto the replication origins through an interaction with the ORC complex in G1 and then travels with the replicative helicase to enable the bypass of fork stalling/blocking lesions. We find that the physical interactions between the Shu complex and replication initiation complexes occurindependently of the other HR machinery including the recombinase Rad51 and the canonical Rad51 paralog, Rad55. Together, our results point to a model where the Shu complex interacts with the replication machinery to enable error-free bypass of DNA damage.