Mechanisms of telomeric instability.
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.
Baird
D M
DM
Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK. bairddm@cardiff.ac.uk
D000705:Anaphase / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics*; D002872:Chromosome Deletion; D004247:DNA / Q000235:genetics*; D004249:DNA Damage; D004261:DNA Replication; D006801:Humans; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics
D034501:Telomere-Binding Proteins; D004247:DNA; D019098:Telomerase