Genetic dissection of parallel sister-chromatid cohesion pathways.

Sister-chromatid cohesion, the process of pairing replicated chromosomes during mitosis and meiosis, is mediated through the essential cohesin complex and a number of nonessential cohesion genes, but the specific roles of these nonessential genes in sister-chromatid cohesion remain to be clarified. We analyzed sister-chromatid cohesion in double mutants of mrc1Delta, tof1Delta, and csm3Delta and identified additive cohesion defects that indicated the existence of at least two pathways that contribute to sister-chromatid cohesion. To understand the relationship of other nonessential cohesion genes with respect to these two pathways, pairwise combinations of deletion and temperature-sensitive alleles were tested for cohesion defects. These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1. Furthermore, we found that the nonessential genes are not important for the maintenance of cohesion at G(2)/M. Thus, our data suggest that nonessential cohesion genes make critical redundant contributions to the establishment of sister-chromatid cohesion and define two cohesion pathways, thereby establishing a framework for understanding the role of nonessential genes in sister-chromatid cohesion.