Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2013 Aug 13;11033:13404-9. doi: 10.1073/pnas.1305020110.
Show Gene links
Show Anatomy links
Aurora B and Cdk1 mediate Wapl activation and release of acetylated cohesin from chromosomes by phosphorylating Sororin.
Nishiyama T, Sykora MM, Huis in 't Veld PJ, Mechtler K, Peters JM.
???displayArticle.abstract???
Sister chromatid cohesion depends on Sororin, a protein that stabilizes acetylated cohesin complexes on DNA by antagonizing the cohesin release factor Wings-apart like protein (Wapl). Cohesion is essential for chromosome biorientation but has to be dissolved to enable sister chromatid separation. To achieve this, the majority of cohesin is removed from chromosome arms in prophase and prometaphase in a manner that depends on Wapl and phosphorylation of cohesin's subunit stromal antigen 2 (SA2), whereas centromeric cohesin is cleaved in metaphase by the protease separase. Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. At centromeres, the cohesin protector shugoshin (Sgo1)-protein phosphatase 2A (PP2A) antagonizes Aurora B and Cdk1 partly by dephosphorylating Sororin and thus maintains cohesion until metaphase. We propose that the stepwise loss of cohesion between chromosome arms and centromeres is caused by local regulation of Wapl activity, which is controlled by the phosphorylation state of Sororin.
Buheitel,
Prophase pathway-dependent removal of cohesin from human chromosomes requires opening of the Smc3-Scc1 gate.
2013, Pubmed
Buheitel,
Prophase pathway-dependent removal of cohesin from human chromosomes requires opening of the Smc3-Scc1 gate.
2013,
Pubmed Chan,
Cohesin's DNA exit gate is distinct from its entrance gate and is regulated by acetylation.
2012,
Pubmed Dreier,
Regulation of sororin by Cdk1-mediated phosphorylation.
2011,
Pubmed Eichinger,
Disengaging the Smc3/kleisin interface releases cohesin from Drosophila chromosomes during interphase and mitosis.
2013,
Pubmed Gandhi,
Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase.
2006,
Pubmed Giménez-Abián,
Regulation of sister chromatid cohesion between chromosome arms.
2004,
Pubmed Hauf,
Cohesin cleavage by separase required for anaphase and cytokinesis in human cells.
2001,
Pubmed Hauf,
The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.
2003,
Pubmed Hauf,
Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2.
2005,
Pubmed Hegemann,
Systematic phosphorylation analysis of human mitotic protein complexes.
2011,
Pubmed Kitajima,
Shugoshin collaborates with protein phosphatase 2A to protect cohesin.
2006,
Pubmed Kueng,
Wapl controls the dynamic association of cohesin with chromatin.
2006,
Pubmed Lafont,
Sororin cooperates with the acetyltransferase Eco2 to ensure DNA replication-dependent sister chromatid cohesion.
2010,
Pubmed
,
Xenbase Lee,
Control of centromere localization of the MEI-S332 cohesion protection protein.
2004,
Pubmed Lénárt,
The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1.
2007,
Pubmed Liu,
Phosphorylation-enabled binding of SGO1-PP2A to cohesin protects sororin and centromeric cohesion during mitosis.
2013,
Pubmed Losada,
Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis.
2002,
Pubmed
,
Xenbase Losada,
Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts.
2005,
Pubmed
,
Xenbase Losada,
Identification of Xenopus SMC protein complexes required for sister chromatid cohesion.
1998,
Pubmed
,
Xenbase McGuinness,
Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells.
2005,
Pubmed Nasmyth,
Cohesin: its roles and mechanisms.
2009,
Pubmed Nishiyama,
Sororin mediates sister chromatid cohesion by antagonizing Wapl.
2010,
Pubmed
,
Xenbase Rankin,
Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates.
2005,
Pubmed
,
Xenbase Riedel,
Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I.
2006,
Pubmed Rolef Ben-Shahar,
Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion.
2008,
Pubmed Schmitz,
Sororin is required for stable binding of cohesin to chromatin and for sister chromatid cohesion in interphase.
2007,
Pubmed Shintomi,
Releasing cohesin from chromosome arms in early mitosis: opposing actions of Wapl-Pds5 and Sgo1.
2009,
Pubmed
,
Xenbase Sumara,
The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase.
2002,
Pubmed
,
Xenbase Tang,
PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation.
2006,
Pubmed Unal,
A molecular determinant for the establishment of sister chromatid cohesion.
2008,
Pubmed Waizenegger,
Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase.
2000,
Pubmed
,
Xenbase Zhang,
Interaction of Sororin protein with polo-like kinase 1 mediates resolution of chromosomal arm cohesion.
2011,
Pubmed Zhang,
Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast.
2008,
Pubmed
