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PLoS Genet. 2014 Oct 16;10(10):e1004680. doi: 10.1371/journal.pgen.1004680. eCollection 2014 Oct.

The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement.

Author information

1
Karolinska Institutet, Department of Cell and Molecular Biology, Stockholm, Sweden.
2
University of Tokyo, Institute of Molecular and Cellular Biosciences, Laboratory of Genome Structure and Function Center for Epigenetic Disease, Bunkyo-ku, Tokyo, Japan.

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.

PMID:
25329383
PMCID:
PMC4199498
DOI:
10.1371/journal.pgen.1004680
[Indexed for MEDLINE]
Free PMC Article

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