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Cytogenet Genome Res. 2008;122(3-4):308-14. doi: 10.1159/000167817. Epub 2009 Jan 30.

Mechanisms of telomeric instability.

Author information

  • 1Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK. bairddm@cardiff.ac.uk

Abstract

Telomeres are the nucleoprotein structures that cap the ends of linear chromosomes. The length of telomeric DNA is an important determinant of function; with short telomeres triggering either replicative senescence or, in the absence of a functional DNA damage response, telomere fusion. Telomere fusion can trigger cycles of anaphase-bridging, breakage and fusion that can lead to genomic arrangements, of the type that are frequently found in cancer. Telomere erosion as a function of ongoing cell division results in the gradual loss of sequences from the terminus; this is superimposed by additional mutational mechanisms that generate large-scale, apparently sporadic, telomeric deletions. These events occur in normal human cells, irrespective of telomerase activity, and because they create telomeres that are capable of fusion, they represent a significant cell-intrinsic mutational mechanism. Here I review some of the potential mechanisms that may result in sporadic telomeric deletion.

PMID:
19188700
DOI:
10.1159/000167817
[PubMed - indexed for MEDLINE]
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