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Persistent telomere cohesion triggers a prolonged anaphase.

Mi Kyung Kim1, Susan Smith

  • 1Kimmel Center for Biology and Medicine at the Skirball Institute, Department of Pathology, New York University School of Medicine, New York, NY 10016.

Molecular Biology of the Cell
|November 1, 2013
PubMed
Summary
This summary is machine-generated.

Persistent telomere cohesion delays anaphase in human and cancer cells. Inhibiting tankyrase 1 or overexpressing TIN2/SA1 increases this cohesion, while tankyrase 1 can rescue the delay, suggesting a balance in telomere integrity.

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Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Telomeres possess unique mechanisms for sister chromatid cohesion, distinct from arms and centromeres.
  • The functional significance of specialized telomere cohesion remains unclear.

Purpose of the Study:

  • To investigate the consequences of persistent telomere sister chromatid cohesion.
  • To elucidate the regulatory mechanisms and cellular responses to excess telomere cohesion.

Main Methods:

  • Fluorescence in situ hybridization (FISH) for visualizing telomeres.
  • Live-cell imaging to observe anaphase progression.
  • Genetic manipulation including protein overexpression and enzyme inhibition (tankyrase 1).

Main Results:

  • Persistent telomere cohesion, induced by tankyrase 1 inhibition or TIN2/SA1 overexpression, prolongs anaphase in normal and cancer cells.
  • Excess telomere cohesion hinders robust and efficient anaphase progression.
  • Overexpression of tankyrase 1 rescues the anaphase delay caused by excess telomere cohesion.
  • Replicatively aged fibroblasts exhibit natural accumulation of telomere cohesion and delayed anaphase, also rescued by tankyrase 1.

Conclusions:

  • Telomere cohesion is regulated by opposing forces, with tankyrase 1 playing a key role in its resolution.
  • Cells employ anaphase delay as a mechanism to tolerate excess telomere cohesion and maintain telomere integrity.
  • This tolerance mechanism may be detrimental in aging but beneficial for cancer cell survival.