Brcl-mediated DNA repair and damage tolerance

The structural maintenance of chromosome (SMC) proteins are key elements in controlling chromosome dynamics. In eukaryotic cells, three essential SMC complexes have been defined: cohesin, condensin, and the Smc5/6 complex. The latter is essential for DNA damage responses; in its absence both repair and checkpoint responses fail. In fission yeast, the UV-C and ionizing radiation (IR) sensitivity of a specific hypomorphic allele encoding the Smc6 subunit, rad18-74 (renamed smc6-74), is suppressed by mild overexpression of a six-BRCT-domain protein, Brcl. Deletion of brcl does not result in a hypersensitivity to UV-C or IR, and thus the function of Brcl relative to the Sinc5/6 complex has remained unclear. Here we show that brcl Delta cells are hypersensitive to a range of radiomimetic drugs that share the feature of creating lesions that are an impediment to the completion of DNA replication. Through a genetic analysis of brcl Delta epistasis and by defining genes required for Brcl to suppress smc6-74, we find that Brcl functions to promote recombination through a novel postreplication repair pathway and the structure-specific nucleases Slx1 and Mus81. Activation of this pathway through overproduction of Brcl bypasses a repair defect in smc6-74, reestablishing resolution of lesions by recombination.