Eroded telomeres are rearranged in quiescent fission yeast cells through duplications of subtelomeric sequences

Laetitia Maestroni,Vincent Géli,Samah Matmati,Stéphane Coulon,Julien Audry,Benoit Arcangioli

doi:10.1038/s41467-017-01894-6

Abstract

While the mechanisms of telomere maintenance has been investigated in dividing cells, little is known about the stability of telomeres in quiescent cells and how dysfunctional telomeres are processed in non-proliferating cells. Here we examine the stability of telomeres in quiescent cells using fission yeast. While wild type telomeres are stable in quiescence, we observe that eroded telomeres were highly rearranged during quiescence in telomerase minus cells. These rearrangements depend on homologous recombination (HR) and correspond to duplications of subtelomeric regions. HR is initiated at newly identified subtelomeric homologous repeated sequences (HRS). We further show that TERRA (Telomeric Repeat-containing RNA) is increased in post-mitotic cells with short telomeres and correlates with telomere rearrangements. Finally, we demonstrate that rearranged telomeres prevent cells to exit properly from quiescence. Taken together, we describe in fission yeast a mode of telomere repair mechanism specific to post-mitotic cells that is likely promoted by transcription.

Highlights

While the mechanisms of telomere maintenance has been investigated in dividing cells, little is known about the stability of telomeres in quiescent cells and how dysfunctional telomeres are processed in non-proliferating cells
In this study, we investigated the stability of eroded telomeres in quiescent fission yeast cells
We demonstrated that these rearrangements, named STEEx, correspond to the amplification of subtelomeric blocks delineated by a homologous repeated sequences (HRS) and are promoted by transcription

Summary

Introduction

While the mechanisms of telomere maintenance has been investigated in dividing cells, little is known about the stability of telomeres in quiescent cells and how dysfunctional telomeres are processed in non-proliferating cells. Base alteration by oxidative stress or other DNA damage may alter the binding of telomeric protein, trigger DNA repair and accelerate the telomere shortening[10,11,12] Whether it concerns postmitotic cells or quiescent stem cells, the observations above raise the question of how telomeres are maintained in quiescence and how the replicative senescence will impact on cell ability to enter and exit quiescence. Cell can survive continually amplifying and rearranging heterochromatic sequences (type III)[21] These survivors are called HAATI (for heterochromatin amplificationmediated and telomerase-independent) and require the heterochromatin assembly machinery, the histone methyl transferase Clr[4]. Subtelomeric sequences (STE) spread from the subtelomeric regions of Chr I and II to multiple sites dispersed in the genome

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Conclusion