Document Detail


Chromosome missegregation in human cells arises through specific types of kinetochore-microtubule attachment errors.
MedLine Citation:
PMID:  21997207     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most solid tumors are aneuploid, and many missegregate chromosomes at high rates in a phenomenon called chromosomal instability (CIN). CIN reflects the erosion of mitotic fidelity, and it correlates with poor patient prognosis and drug resistance. The most common mechanism causing CIN is the persistence of improper kinetochore-microtubule attachments called merotely. Chromosomes with merotelic kinetochores often manifest as lagging chromosomes in anaphase, suggesting that lagging chromosomes fail to segregate properly. However, it remains unknown whether the lagging chromosomes observed in anaphase segregate to the correct or incorrect daughter cell. To address this question, we tracked the segregation of a single human chromosome during cell division by using LacI-GFP to target an integrated LacO array. By scoring the distribution of each sister chromatid during mitosis, we show that a majority of lagging chromosomes in anaphase segregate to the correct daughter cell. Instead, sister chromatids that segregate erroneously frequently do so without obvious evidence of lagging during anaphase. This outcome is expected if sister kinetochores on a chromosome bind microtubules oriented toward the same spindle pole, and we find evidence for syntelic kinetochore attachments in cells after treatments that increase missegregation rates. Thus, lagging chromosomes in anaphase are symptomatic of defects in kinetochore-microtubule attachment dynamics that cause chromosome missegregation associated with CIN, but the laggards rarely missegregate.
Authors:
Sarah L Thompson; Duane A Compton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-02     Completed Date:  2012-01-09     Revised Date:  2013-07-31    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17974-8     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Chromosome Segregation*
Humans
Kinetochores / metabolism*
Microtubules / metabolism*
Grant Support
ID/Acronym/Agency:
GM008704/GM/NIGMS NIH HHS; GM51542/GM/NIGMS NIH HHS; P30 CA023108/CA/NCI NIH HHS; R01 GM051542/GM/NIGMS NIH HHS; T32 GM008704/GM/NIGMS NIH HHS
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