title: Regulation of telomere addition at DNA double-strand breaks.
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.
authors.affiliation: Department of Molecular Biology, National Center for Competence in Research NCCR program Frontiers in Genetics, University of Geneva, 30 quai Ernest-Ansermet, 1211, Geneva 4, Switzerland. cyril.ribeyre@igh.cnrs.fr
authors.forename: Cyril
authors.initials: C
authors.lastname: Ribeyre
authors.forename: David
authors.initials: D
authors.lastname: Shore
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D005786:Gene Expression Regulation; D006801:Humans; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
chemical_list: D019098:Telomerase