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| Subject Categories: Genome Stability & Dynamics |
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| The EMBO Journal
(2007) 26, 4867–4878, doi:10.1038/sj.emboj.7601903 Published online 25 October 2007 |
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| Protein requirements for sister telomere association in human cells |
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| Silvia Canudas, Benjamin R Houghtaling1, Ju Youn Kim, Jasmin N Dynek2, William G Chang3 and Susan Smith |
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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, USA To whom correspondence should be addressed Susan Smith, Program in Molecular Pathogenesis and Department of Pathology, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Tel.: +1 212 263 2540; Fax: +1 212 263 5711; E-mail: smithsu@saturn.med.nyu.edu 1 Present address: Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065, USA 2 Present address: Department of Protein Engineering, Genentech Inc., South San Francisco, CA 94080, USA 3 Present address: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Received 21 June 2007; Accepted 4 October 2007; Published online 25 October 2007. |
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| Abstract |
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| 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. |
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| Keywords: cohesins, sister chromatids, tankyrase 1, telomeres, TRF1 |
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