Zhdanova N S, Draskovic I, Minina J M, Karamysheva T V, Novo C L, Liu W-Y, Porreca R M, Gibaud A, Zvereva M E, Skvortsov D A, Rubtsov N B, Londoño-Vallejo A
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
Telomere & Cancer Laboratory, Equipe Labelisée Ligue Nationale contre le Cancer, Institut Curie, Paris, and UPMC University Paris, Paris, France.
Mol Cell Biol. 2014 Aug;34(15):2786-99. doi: 10.1128/MCB.01697-13. Epub 2014 May 19.
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.
伊比利亚鼩鼱（Sorex granarius）的端粒结构具有独特而显著的特征，近端着丝粒染色体的短臂携带极长的端粒（长达300 kb），其中散布着核糖体DNA（rDNA）重复序列块。在这项研究中，我们研究了伊比利亚鼩鼱成纤维细胞的端粒生理学，发现端粒重复序列在两条链上都有转录，并且不存在端粒依赖性衰老机制。尽管在整个细胞培养过程中都可检测到端粒酶活性，并且它似乎对短端粒和长端粒都起作用，但我们还发现重组活性的特征无处不在，包括端粒-姐妹染色单体交换、端粒替代延长（ALT）相关的PML样体的形成、端粒环的产生，以及携带DNA损伤反应标记的端粒的高频率出现。我们的结果表明，重组参与了正常伊比利亚鼩鼱成纤维细胞中非常长的端粒的维持。我们讨论了在该生物体中，散布的端粒和rDNA重复序列在极长端粒稳定化过程中可能的相互作用。
