title: H2A.Z-dependent regulation of cohesin dynamics on chromosome arms.
abstract: Structural maintenance of chromosomes (SMC) complexes and DNA topoisomerases are major determinants of chromosome structure and dynamics. The cohesin complex embraces sister chromatids throughout interphase, but during mitosis most cohesin is stripped from chromosome arms by early prophase, while the remaining cohesin at kinetochores is cleaved at anaphase. This two-step removal of cohesin is required for sister chromatids to separate. The cohesin-related Smc5/6 complex has been studied mostly as a determinant of DNA repair via homologous recombination. However, chromosome segregation fails in Smc5/6 null mutants or cells treated with small interfering RNAs. This also occurs in Smc5/6 hypomorphs in the fission yeast Schizosaccharomyces pombe following genotoxic and replication stress, or topoisomerase II dysfunction, and these mitotic defects are due to the postanaphase retention of cohesin on chromosome arms. Here we show that mitotic and repair roles for Smc5/6 are genetically separable in S. pombe. Further, we identified the histone variant H2A.Z as a critical factor to modulate cohesin dynamics, and cells lacking H2A.Z suppress the mitotic defects conferred by Smc5/6 dysfunction. Together, H2A.Z and the SMC complexes ensure genome integrity through accurate chromosome segregation.
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tapia-Alveal
authors.forename: Su-Jiun
authors.initials: SJ
authors.lastname: Lin
authors.forename: Aaron
authors.initials: A
authors.lastname: Yeoh
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Jabado
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: O'Connell
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D015825:Chromosomes, Fungal / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D034622:RNA Interference; D034741:RNA, Small Interfering; 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; D006657:Histones; D034741:RNA, Small Interfering; D029702:Schizosaccharomyces pombe Proteins; D000097722:Cohesins; C091242:PHT1 protein, S pombe; C486628:Smc5 protein, S pombe; C077020:histone H2A.F-Z; C486630:smc6 protein, S pombe