The Chromosomal Association of the Smc5/6 Complex Depends on Cohesion and Predicts the Level of Sister Chromatid Entanglement e1004680

• Published in: PLoS genetics Vol. 10; no. 10
• Main Authors: Jeppsson, Kristian, Carlborg, Kristian K, Nakato, Ryuichiro, Berta, Davide G, Lilienthal, Ingrid, Kanno, Takaharu, Lindqvist, Arne, Brink, Maartje C, Dantuma, Nico P, Katou, Yuki, Shirahige, Katsuhiko, Sjögren, Camilla
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.10.2014
• Subjects: Binding sites; Chromatin; Chromosomes; Deoxyribonucleic acid; DNA; Genomics; Proteins; Saccharomyces cerevisiae; Yeast
• ISSN: 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004680

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.