title: SMC complexes and topoisomerase II work together so that sister chromatids can work apart.
abstract: The pairing of sister chromatids in interphase facilitates error-free homologous recombination (HR). Sister chromatids are held together by cohesin, one of three Structural Maintenance of Chromosomes (SMC) complexes. In mitosis, chromosome condensation is controlled by another SMC complex, condensin, and the type II topoisomerase (Top2). In prophase, cohesin is stripped from chromosome arms, but remains at centromeres until anaphase, whereupon it is removed via proteolytic cleavage. The third SMC complex, Smc5/6, is generally described as a regulator of HR-mediated DNA repair. However, cohesin and condensin are also required for DNA repair, and HR genes are not essential for cell viability, but the SMC complexes are. Smc5/6 null mutants die in mitosis, and in fission yeast, Smc5/6 hypomorphs show lethal mitoses following genotoxic stress, or when combined with a Top2 mutant, top2-191. We found these mitotic defects are due to retention of cohesin on chromosome arms. We also show that Top2 functions in the cohesin cycle, and accumulating data suggests this is not related to its decatenation activity. Thus the SMC complexes and Top2 functionally interact, and any DNA repair function ascribed to Smc5/6 is likely a reflection of a more fundamental role in the regulation of chromosome structure.
authors.affiliation: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tapia-Alveal
authors.forename: Emily A
authors.initials: EA
authors.lastname: Outwin
authors.forename: Natalia
authors.initials: N
authors.lastname: Trempolec
authors.forename: Dorota
authors.initials: D
authors.lastname: Dziadkowiec
authors.forename: Johanne M
authors.initials: JM
authors.lastname: Murray
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: O'Connell
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D042822:Genomic Instability; D008938:Mitosis; D009154:Mutation; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004250:DNA Topoisomerases, Type II; D029702:Schizosaccharomyces pombe Proteins; D000097722:Cohesins; C486628:Smc5 protein, S pombe; C486630:smc6 protein, S pombe