Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1
Ring-shaped cohesin keeps sister chromatids paired until cleavage of its Scc1/Rad21 subunit by separase triggers chromosome segregation in anaphase. Vertebrate separase is held inactive by mutually exclusive binding to securin or Cdk1-cyclin B1 and becomes unleashed only upon ubiquitin-dependent deg...
| Main Authors: | , , , , , |
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| Format: | Journal article |
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Elsevier
2015
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| _version_ | 1797087272408973312 |
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| author | Hellmuth, S Rata, S Brown, A Heidmann, S Novak, B Stemmann, O |
| author_facet | Hellmuth, S Rata, S Brown, A Heidmann, S Novak, B Stemmann, O |
| author_sort | Hellmuth, S |
| collection | OXFORD |
| description | Ring-shaped cohesin keeps sister chromatids paired until cleavage of its Scc1/Rad21 subunit by separase triggers chromosome segregation in anaphase. Vertebrate separase is held inactive by mutually exclusive binding to securin or Cdk1-cyclin B1 and becomes unleashed only upon ubiquitin-dependent degradation of these regulators. Although most separase is usually found in association with securin, this anaphase inhibitor is dispensable for murine life while Cdk1-cyclin B1-dependent control of separase is essential. Here, we show that securin-independent inhibition of separase by Cdk1-cyclin B1 in early mitosis requires the phosphorylation-specific peptidyl-prolyl cis/trans isomerase Pin1. Furthermore, isomerization of previously securin-bound separase at the metaphase-to-anaphase transition renders it resistant to re-inhibition by residual securin. At the same time, isomerization also limits the half-life of separase's proteolytic activity, explaining how cohesin can be reloaded onto telophase chromatin in the absence of securin and cyclin B1 without being cleaved. |
| first_indexed | 2024-03-07T02:33:29Z |
| format | Journal article |
| id | oxford-uuid:a804d473-b6cf-4bf6-b693-6d15951e9f3c |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:33:29Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:a804d473-b6cf-4bf6-b693-6d15951e9f3c2022-03-27T02:58:30ZHuman chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a804d473-b6cf-4bf6-b693-6d15951e9f3cSymplectic Elements at OxfordElsevier2015Hellmuth, SRata, SBrown, AHeidmann, SNovak, BStemmann, ORing-shaped cohesin keeps sister chromatids paired until cleavage of its Scc1/Rad21 subunit by separase triggers chromosome segregation in anaphase. Vertebrate separase is held inactive by mutually exclusive binding to securin or Cdk1-cyclin B1 and becomes unleashed only upon ubiquitin-dependent degradation of these regulators. Although most separase is usually found in association with securin, this anaphase inhibitor is dispensable for murine life while Cdk1-cyclin B1-dependent control of separase is essential. Here, we show that securin-independent inhibition of separase by Cdk1-cyclin B1 in early mitosis requires the phosphorylation-specific peptidyl-prolyl cis/trans isomerase Pin1. Furthermore, isomerization of previously securin-bound separase at the metaphase-to-anaphase transition renders it resistant to re-inhibition by residual securin. At the same time, isomerization also limits the half-life of separase's proteolytic activity, explaining how cohesin can be reloaded onto telophase chromatin in the absence of securin and cyclin B1 without being cleaved. |
| spellingShingle | Hellmuth, S Rata, S Brown, A Heidmann, S Novak, B Stemmann, O Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1 |
| title | Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1 |
| title_full | Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1 |
| title_fullStr | Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1 |
| title_full_unstemmed | Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1 |
| title_short | Human chromosome segregation involves multi-layered regulation of separase by the peptidyl-prolyl-isomerase Pin 1 |
| title_sort | human chromosome segregation involves multi layered regulation of separase by the peptidyl prolyl isomerase pin 1 |
| work_keys_str_mv | AT hellmuths humanchromosomesegregationinvolvesmultilayeredregulationofseparasebythepeptidylprolylisomerasepin1 AT ratas humanchromosomesegregationinvolvesmultilayeredregulationofseparasebythepeptidylprolylisomerasepin1 AT browna humanchromosomesegregationinvolvesmultilayeredregulationofseparasebythepeptidylprolylisomerasepin1 AT heidmanns humanchromosomesegregationinvolvesmultilayeredregulationofseparasebythepeptidylprolylisomerasepin1 AT novakb humanchromosomesegregationinvolvesmultilayeredregulationofseparasebythepeptidylprolylisomerasepin1 AT stemmanno humanchromosomesegregationinvolvesmultilayeredregulationofseparasebythepeptidylprolylisomerasepin1 |