Protein requirements for sister telomere association in human cells

EMBO J. 2007 Nov 28;26(23):4867-78. doi: 10.1038/sj.emboj.7601903. Epub 2007 Oct 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Tankyrases / metabolism
  • Telomere / ultrastructure*
  • Telomere-Binding Proteins / metabolism
  • Telomeric Repeat Binding Protein 1 / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • TINF2 protein, human
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 1
  • cohesins
  • Poly(ADP-ribose) Polymerases
  • Tankyrases
  • TNKS protein, human