Document Detail


Age-dependent susceptibility of chromosome cohesion to premature separase activation in mouse oocytes.
MedLine Citation:
PMID:  21865557     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A hypothesis to explain the maternal age-dependent increase in formation of aneuploid eggs is deterioration of chromosome cohesion. Although several lines of evidence are consistent with this hypothesis, whether cohesion is actually reduced in naturally aged oocytes has not been directly tested by any experimental perturbation. To directly target cohesion, we increased the activity of separase, the protease that cleaves the meiotic cohesin REC8, in oocytes. We show that cohesion is more susceptible to premature separase activation in old oocytes than in young oocytes, demonstrating that cohesion is significantly reduced. Furthermore, cohesion is protected by two independent mechanisms that inhibit separase, securin and an inhibitory phosphorylation of separase by CDK1; both mechanisms must be disrupted to prematurely activate separase. With the continual loss of cohesins from chromosomes that occurs throughout the natural reproductive lifespan, tight regulation of separase in oocytes may be particularly important to maintain cohesion and prevent aneuploidy.
Authors:
Teresa Chiang; Richard M Schultz; Michael A Lampson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-24
Journal Detail:
Title:  Biology of reproduction     Volume:  85     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-25     Completed Date:  2012-04-12     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1279-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Animals
Cell Cycle Proteins / metabolism*
Chromosomes / physiology*
Endopeptidases / metabolism*
Female
Mice
Nuclear Proteins / metabolism*
Oocytes / physiology*
Phosphoproteins / metabolism*
Separase
Grant Support
ID/Acronym/Agency:
HD 058730/HD/NICHD NIH HHS; R01 HD058730/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Nuclear Proteins; 0/Phosphoproteins; 0/Rec8 protein, mouse; EC 3.4.-/Endopeptidases; EC 3.4.22.49/Separase
Comments/Corrections

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