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Genome Biol. 2007;8(12):R260.

Contribution of telomerase RNA retrotranscription to DNA double-strand break repair during mammalian genome evolution.

Author information

  • 1Dipartimento di Genetica e Microbiologia 'Adriano Buzzati-Traverso', Universit√† degli Studi di Pavia, Via Ferrata, 27100 Pavia, Italy.

Abstract

BACKGROUND:

In vertebrates, tandem arrays of TTAGGG hexamers are present at both telomeres and intrachromosomal sites (interstitial telomeric sequences (ITSs)). We previously showed that, in primates, ITSs were inserted during the repair of DNA double-strand breaks and proposed that they could arise from either the capture of telomeric fragments or the action of telomerase.

RESULTS:

An extensive comparative analysis of two primate (Homo sapiens and Pan troglodytes) and two rodent (Mus musculus and Rattus norvegicus) genomes allowed us to describe organization and insertion mechanisms of all the informative ITSs present in the four species. Two novel observations support the hypothesis of telomerase involvement in ITS insertion: in a highly significant fraction of informative loci, the ITSs were introduced at break sites where a few nucleotides homologous to the telomeric hexamer were exposed; in the rodent genomes, complex ITS loci are present in which a retrotranscribed fragment of the telomerase RNA, far away from the canonical template, was inserted together with the telomeric repeats. Moreover, mutational analysis of the TTAGGG arrays in the different species suggests that they were inserted as exact telomeric hexamers, further supporting the participation of telomerase in ITS formation.

CONCLUSION:

These results strongly suggest that telomerase was utilized, in some instances, for the repair of DNA double-strand breaks occurring in the genomes of rodents and primates during evolution. The presence, in the rodent genomes, of sequences retrotranscribed from the telomerase RNA strengthens the hypothesis of the origin of telomerase from an ancient retrotransposon.

PMID:
18067655
[PubMed - indexed for MEDLINE]
PMCID:
PMC2246262
Free PMC Article

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