Document Detail


Protein requirements for sister telomere association in human cells.
MedLine Citation:
PMID:  17962804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies in human cells indicate that sister telomeres have distinct requirements for their separation at mitosis. In cells depleted for tankyrase 1, a telomeric poly(ADP-ribose) polymerase, sister chromatid arms and centromeres separate normally, but telomeres remain associated and cells arrest in mitosis. Here, we use biochemical and genetic approaches to identify proteins that might mediate the persistent association at sister telomeres. We use immunoprecipitation analysis to show that the telomeric proteins, TRF1 (an acceptor of PARsylation by tankyrase 1) and TIN2 (a TRF1 binding partner) each bind to the SA1 ortholog of the cohesin Scc3 subunit. Sucrose gradient sedimentation shows that TRF1 cosediments with the SA1-cohesin complex. Depletion of the SA1 cohesin subunit or the telomeric proteins (TRF1 and TIN2) restores the normal resolution of sister telomeres in mitosis in tankyrase 1-depleted cells. Moreover, depletion of TRF1 and TIN2 or SA1 abrogates the requirement for tankyrase 1 in mitotic progression. Our studies indicate that sister telomere association in human cells is mediated by a novel association between a cohesin subunit and components of telomeric chromatin.
Authors:
Silvia Canudas; Benjamin R Houghtaling; Ju Youn Kim; Jasmin N Dynek; William G Chang; Susan Smith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-10-25
Journal Detail:
Title:  The EMBO journal     Volume:  26     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-28     Completed Date:  2007-12-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  4867-78     Citation Subset:  IM    
Affiliation:
Program in Molecular Pathogenesis and Department of Pathology, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle Proteins / metabolism
Centrifugation, Density Gradient
Chromosomal Proteins, Non-Histone / metabolism
Gene Expression Regulation, Neoplastic
Hela Cells
Humans
Immunoprecipitation
In Situ Hybridization, Fluorescence
Mitosis
Models, Biological
Nuclear Proteins / metabolism
Poly(ADP-ribose) Polymerases / metabolism
Protein Binding
Tankyrases / genetics,  metabolism
Telomere / ultrastructure*
Telomere-Binding Proteins / metabolism
Telomeric Repeat Binding Protein 1 / metabolism
Grant Support
ID/Acronym/Agency:
CA09161/CA/NCI NIH HHS; GM07238/GM/NIGMS NIH HHS; R01 CA116352/CA/NCI NIH HHS; R01 CA95099/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Chromosomal Proteins, Non-Histone; 0/Nuclear Proteins; 0/TINF2 protein, human; 0/Telomere-Binding Proteins; 0/Telomeric Repeat Binding Protein 1; 0/cohesins; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.4.2.30/Tankyrases; EC 2.4.4.30/TNKS protein, human
Comments/Corrections

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