Abstract
Homologous recombination (HR) is important for DNA damage tolerance during replication. The yeast Shu complex, a conserved homologous recombination factor, prevents replication-associated mutagenesis. Here we examine how yeast cells require the Shu complex for coping with MMS-induced lesions during DNA replication. We find that Csm2, a subunit of the Shu complex, binds to autonomous-replicating sequences (ARS) in yeast. Further evolutionary studies reveal that the yeast and human Shu complexes have co-evolved with specific replication-initiation factors. The connection between the Shu complex and replication is underlined by the finding that the Shu complex interacts with the ORC and MCM complexes. For example, the Shu complex interacts, independent of other HR proteins, with the replication initiation complexes through the N-terminus of Psy3. Lastly, we show interactions between the Shu complex and the replication initiation complexes are essential for resistance to DNA damage, to prevent mutations and aberrant recombination events. In our model, the Shu complex interacts with the replication machinery to enable error-free bypass of DNA damage.