Regulation of telomere addition at DNA double-strand breaks
- 17 March 2013
- journal article
- review article
- Published by Springer Science and Business Media LLC in Chromosoma
- Vol. 122 (3), 159-173
- https://doi.org/10.1007/s00412-013-0404-2
Abstract
Telomeres constitute the ends of linear eukaryotic chromosomes. Due to the conventional mode of DNA replication, telomeric DNA erodes at each cell division. To counteract this, a specialized reverse transcriptase, telomerase, can elongate chromosome ends to maintain them at a constant average length. Because of their similarity to DNA double-strand breaks (DSBs), telomeres might be expected to induce a DNA damage response, which would lead to repair reactions and the generation of translocations or fusions. Many proteins present at telomeres prevent this by protecting (capping) the chromosome termini. Conversely, a DSB occurring in other regions of the genome, due, for instance, to a stalled replication fork or genotoxic agents, must be repaired by homologous recombination or end-joining to ensure genome stability. Interestingly, telomerase is able to generate a telomere de novo at an accidental DSB, with potentially lethal consequences in haploid cells and, at a minimum, loss of heterozygosity (LOH) in diploid cells. Recent data suggest that telomerase is systematically recruited to DSBs but is prevented from acting in the absence of a minimal stretch of flanking telomere-repeat sequences. In this review, we will focus on the mechanisms that regulate telomere addition to DSBs.Keywords
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