Marseille Cancer Research Center (CRCM), CNRS, INSERM, Aix Marseille Univ, Institut Paoli-Calmettes, Equipe labélisée Ligue contre le cancer, 13273, Marseille, France.
Dynamics of the Genome, UMR 3225 Genomes & Genetics; Institut Pasteur, 75015, Paris, France.
Nat Commun. 2017 Nov 22;8(1):1684. doi: 10.1038/s41467-017-01894-6.
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.
虽然端粒维持的机制在分裂细胞中已经得到了研究,但对于静止细胞中端粒的稳定性以及非增殖细胞中端粒功能失调是如何被处理的,人们知之甚少。在这里,我们使用裂殖酵母来研究静止细胞中端粒的稳定性。虽然野生型端粒在静止期是稳定的,但我们观察到在端粒酶缺失的细胞中,在静止期,侵蚀的端粒发生了高度重排。这些重排依赖于同源重组(HR),并对应于端粒区的重复。HR 是在新鉴定的端粒旁同源重复序列(HRS)处起始的。我们进一步表明,端粒重复 RNA(TERRA)在端粒较短的有丝分裂后细胞中增加,并与端粒重排相关。最后,我们证明了重排的端粒阻止细胞正常从静止状态中退出。总之,我们在裂殖酵母中描述了一种特定于有丝分裂后细胞的端粒修复机制,这种机制可能是由转录所促进的。