Abstract
The Mus81-Eme1 complex was proposed to be an essential component of a Holliday junction resolvase. A subsequent study showed, however, that the complex preferentially cleaves 3-flap structures and replication forks rather than intact Holliday junctions, suggesting that Mus81-Eme1 may play a role in replication fork processing and repair. A more recent study has shown that Rad51C or Rad51C-associated proteins are involved in the resolution of intact Holliday junctions in mammals. Despite accumulating evidence for the role of Mus81 in the processing of recombination intermediates, biological functions of the protein in mammals remain to be demonstrated. To help define the roles of Mus81 and Rad51C in human cells, we deleted the genes in the human colon cancer cell line. Here we show that these genes are essential for mitotic homologous recombination. Furthermore, defective recombination repair resulted in checkpoint activation. This finding provides direct evidence for the roles of Mus81 and Rad51 paralogs in the maintenance of chromosome stability through coupling the recombination machinery with the unprocessed intermediates-dependent checkpoint pathway.
