title: The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement.
abstract: The cohesin complex, which is essential for sister chromatid cohesion and chromosome segregation, also inhibits resolution of sister chromatid intertwinings (SCIs) by the topoisomerase Top2. The cohesin-related Smc5/6 complex (Smc5/6) instead accumulates on chromosomes after Top2 inactivation, known to lead to a buildup of unresolved SCIs. This suggests that cohesin can influence the chromosomal association of Smc5/6 via its role in SCI protection. Using high-resolution ChIP-sequencing, we show that the localization of budding yeast Smc5/6 to duplicated chromosomes indeed depends on sister chromatid cohesion in wild-type and top2-4 cells. Smc5/6 is found to be enriched at cohesin binding sites in the centromere-proximal regions in both cell types, but also along chromosome arms when replication has occurred under Top2-inhibiting conditions. Reactivation of Top2 after replication causes Smc5/6 to dissociate from chromosome arms, supporting the assumption that Smc5/6 associates with a Top2 substrate. It is also demonstrated that the amount of Smc5/6 on chromosomes positively correlates with the level of missegregation in top2-4, and that Smc5/6 promotes segregation of short chromosomes in the mutant. Altogether, this shows that the chromosomal localization of Smc5/6 predicts the presence of the chromatid segregation-inhibiting entities which accumulate in top2-4 mutated cells. These are most likely SCIs, and our results thus indicate that, at least when Top2 is inhibited, Smc5/6 facilitates their resolution.
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Jeppsson
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Kristian K
authors.initials: KK
authors.lastname: Carlborg
authors.affiliation: University of Tokyo, Institute of Molecular and Cellular Biosciences, Laboratory of Genome Structure and Function Center for Epigenetic Disease, Bunkyo-ku, Tokyo, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nakato
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Davide G
authors.initials: DG
authors.lastname: Berta
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lilienthal
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Lindqvist
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Maartje C
authors.initials: MC
authors.lastname: Brink
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Nico P
authors.initials: NP
authors.lastname: Dantuma
authors.affiliation: University of Tokyo, Institute of Molecular and Cellular Biosciences, Laboratory of Genome Structure and Function Center for Epigenetic Disease, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katou
authors.affiliation: University of Tokyo, Institute of Molecular and Cellular Biosciences, Laboratory of Genome Structure and Function Center for Epigenetic Disease, Bunkyo-ku, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.affiliation: Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Sjögren
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000378:metabolism*; D053960:DNA Breaks; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004250:DNA Topoisomerases, Type II; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae