Abstract

Interstitial telomeric sequences (ITSs) are stretches of telomeric-like repeats located at internal chromosomal sites. We previously demonstrated that ITSs have been inserted during the repair of DNA double-strand breaks in the course of evolution and that some rodent ITSs, called TERC-ITSs, are flanked by fragments retrotranscribed from the telomerase RNA component (TERC). In this work, we carried out an extensive search of TERC-ITSs in 30 vertebrate genomes and identified 41 such loci in 22 species, including in humans and other primates. The fragment retrotranscribed from the TERC RNA varies in different lineages and its sequence seems to be related to the organization of TERC. Through comparative analysis of TERC-ITSs with orthologous empty loci, we demonstrated that, at each locus, the TERC-like sequence and the ITS have been inserted in one step in the course of evolution. Our findings suggest that telomerase participated in a peculiar pathway of DNA double-strand break repair involving retrotranscription of its RNA component and that this mechanism may be active in all vertebrate species. These results add new evidence to the hypothesis that RNA-templated DNA repair mechanisms are active in vertebrate cells.

Highlights

  • Accepted: 11 October 2021Telomeres are specialized nucleoprotein structures located at the termini of linear chromosomes

  • We demonstrated that, in the mouse and rat genome, the generation of telomerase RNA component (TERC)-Interstitial telomeric sequences (ITSs) occurred during the repair of DNA double-strand breaks and involved the insertion of fragments retrotranscribed from the telomerase RNA [34,35]

  • We searched for TERC-ITS loci in the genome of 30 vertebrate species that were selected from different orders on the basis of the availability of well assembled genomic sequences and an identifiable TERC gene

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Summary

Introduction

Telomeres are specialized nucleoprotein structures located at the termini of linear chromosomes. The main function of telomeres is to protect the ends of chromosomes by differentiating them from DNA double-strand breaks [1]. Telomeres are composed of tandem arrays of the TTAGGG hexanucleotide which are associated with a protein complex called shelterin and with other accessory proteins [1]. Telomeres are transcribed into a family of noncoding telomeric repeat-containing RNA (TERRA). The association of telomeric DNA with proteins and TERRA is essential for the maintenance of telomere structure and function [3]. Deregulation of TERRA expression has been proposed as a marker for tumor progression [4,5]

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