Processing of homologous recombination repair intermediates by the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes

Homologous recombination repair (HRR) is an evolutionarily conserved cellular process that is important for the maintenance of genome stability during S-phase. Inactivation of the Saccharomyces cerevisiae Sgs1-Top3-Rmi1 complex leads to the accumulation of unprocessed, X-shaped HRR intermediates (X-structures) following replicative stress. Further characterization of these X-structures may reveal why loss of BLM (the human Sgs1 ortholog) leads to the human cancer-predisposition disorder, Bloom's syndrome. In two recent complementary studies, we examined the nature of the X-structures arising in yeast strains lacking Sgs1, Top3 or Rmi1, by identifying which proteins could process these structures in vivo. We revealed that the unprocessed X-structures that accumulate in these strains could be resolved by the ectopic overexpression of two different Holliday junction (HJ) resolvases, and that the endogenous Mus81-Mms4 endonuclease could also remove them, albeit slowly. In this review, we discuss the implications of these results and review the putative roles for the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes in the processing of various types of HRR intermediates during S phase.