Recombinogenic Telomeres in Diploid Sorex granarius (Soricidae, Eulipotyphla) Fibroblast Cells

Abstract

The telomere structure in the Iberian shrew Sorex granarius is characterized by unique, striking features, with short arms of acrocentric chromosomes carrying extremely long telomeres (up to 300 kb) with interspersed ribosomal DNA (rDNA) repeat blocks. In this work, we investigated the telomere physiology of S. granarius fibroblast cells and found that telomere repeats are transcribed on both strands and that there is no telomere-dependent senescence mechanism. Although telomerase activity is detectable throughout cell culture and appears to act on both short and long telomeres, we also discovered that signatures of a recombinogenic activity are omnipresent, including telomere-sister chromatid exchanges, formation of alternative lengthening of telomeres (ALT)-associated PML-like bodies, production of telomere circles, and a high frequency of telomeres carrying marks of a DNA damage response. Our results suggest that recombination participates in the maintenance of the very long telomeres in normal S. granarius fibroblasts. We discuss the possible interplay between the interspersed telomere and rDNA repeats in the stabilization of the very long telomeres in this organism.

ACKNOWLEDGMENTS

This work was partly supported by a budgetary project of the Institute of Cytology and Genetics of SB RAS VI.53.1.4, Project RAS “Living nature: modern status and problems of development” 30-32, and by the CNRS, through the PIC program. C.L.N. was a recipient of a fellowship from the Institut Curie. R.M.P. obtained a Ph.D. fellowship from the Institut Curie and Association pour la Recherche contre le Cancer. The Telomere & Cancer Laboratory is supported by the Ligue Nationale contre le Cancer.