Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour formation

Ling Qi, Margaret A. Strong, Baktiar O. Karim, David L. Huso, Carol W. Greider

Research output: Contribution to journalArticlepeer-review

Abstract

Telomeres protect chromosome ends from fusion, degradation and recombination. Loss of telomere function has opposite effects on tumorigenesis: apoptosis, which inhibits tumour growth, and genomic instability, which accelerates tumour formation. Here we describe a new mechanism by which short telomeres inhibit tumorigenesis through interference with oncogenic translocations. In mice that are null for both ataxia-telangiectasia-mutated (Atm) and telomerase RNA (mTR), the first generation (G1) Atm-/- mTR-/- mice have a lower rate of tumour formation than Atm-/- mTR+/+ mice. These Atm-/- mTR-/- G1 tumours show no increase in either apoptosis or overall genomic instability. Strikingly, the tumours show a high fraction of translocations containing telomere signals at the translocation junctions. Translocations of the T-cell receptors on chromosome 14, which initiate tumorigenesis, were interrupted by fusion with telomeres. Telomere repeats were also detected at the translocation junctions in pre-malignant thymocytes. We propose that telomere fusion to DNA double-strand breaks competes with the generation of oncogenic translocations and thus reduces tumour formation.

Original languageEnglish (US)
Pages (from-to)706-711
Number of pages6
JournalNature cell biology
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Cell Biology

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