title: Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae.
abstract: Cohesins are required both for the tethering together of sister chromatids (termed cohesion) and subsequent condensation into discrete structures-processes fundamental for faithful chromosome segregation into daughter cells. Differentiating between cohesin roles in cohesion and condensation would provide an important advance in studying chromatin metabolism. Pds5 is a cohesin-associated factor that is essential for both cohesion maintenance and condensation. Recent studies revealed that ELG1 deletion suppresses the temperature sensitivity of pds5 mutant cells. However, the mechanisms through which Elg1 may regulate cohesion and condensation remain unknown. Here, we report that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast, RAD61 deletion rescues the condensation defect, but importantly, neither the temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In combination, these findings reveal that cohesion and condensation are separable pathways and regulated in nonredundant mechanisms. These results are discussed in terms of a new model through which cohesion and condensation are spatially regulated.
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tong
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015 RVS3@Lehigh.edu.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Skibbens
mesh_terms: D000704:Analysis of Variance; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D008853:Microscopy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D018809:Proliferating Cell Nuclear Antigen; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C477609:Elg1 protein, S cerevisiae; C427726:PDS5 protein, S cerevisiae; C476199:RAD61 protein, S cerevisiae
keywords: Elg1 and PCNA; Rad61/WAPL; chromosome condensation; cohesin; sister chromatid cohesion