The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement.
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-10-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4199498?pdf=render |
| _version_ | 1818516695923294208 |
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| author | Kristian Jeppsson Kristian K Carlborg Ryuichiro Nakato Davide G Berta Ingrid Lilienthal Takaharu Kanno Arne Lindqvist Maartje C Brink Nico P Dantuma Yuki Katou Katsuhiko Shirahige Camilla Sjögren |
| author_facet | Kristian Jeppsson Kristian K Carlborg Ryuichiro Nakato Davide G Berta Ingrid Lilienthal Takaharu Kanno Arne Lindqvist Maartje C Brink Nico P Dantuma Yuki Katou Katsuhiko Shirahige Camilla Sjögren |
| author_sort | Kristian Jeppsson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T00:45:40Z |
| format | Article |
| id | doaj.art-6d6b6b3ed64b4e3f858e274984a86849 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T00:45:40Z |
| publishDate | 2014-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-6d6b6b3ed64b4e3f858e274984a868492022-12-22T01:26:46ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-10-011010e100468010.1371/journal.pgen.1004680The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement.Kristian JeppssonKristian K CarlborgRyuichiro NakatoDavide G BertaIngrid LilienthalTakaharu KannoArne LindqvistMaartje C BrinkNico P DantumaYuki KatouKatsuhiko ShirahigeCamilla SjögrenThe 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.http://europepmc.org/articles/PMC4199498?pdf=render |
| spellingShingle | Kristian Jeppsson Kristian K Carlborg Ryuichiro Nakato Davide G Berta Ingrid Lilienthal Takaharu Kanno Arne Lindqvist Maartje C Brink Nico P Dantuma Yuki Katou Katsuhiko Shirahige Camilla Sjögren The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. PLoS Genetics |
| title | The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. |
| title_full | The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. |
| title_fullStr | The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. |
| title_full_unstemmed | The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. |
| title_short | The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. |
| title_sort | chromosomal association of the smc5 6 complex depends on cohesion and predicts the level of sister chromatid entanglement |
| url | http://europepmc.org/articles/PMC4199498?pdf=render |
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