Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA
复制标题
DOI：
10.1093/nar/gkv296
复制
发表时间：
2015-05-19
影响因子：
14.9
通讯作者：
Trantirek, Lukas
中科院分区：
文献类型：
--
作者：
Skolakova, Petra;Foldynova-Trantirkova, Silvie;Trantirek, Lukas
有两种基本机制与端粒长度的维持有关，端粒长度赋予癌细胞无限的增殖潜力。一种机制，称为端粒的替代性延长（ALT），占所有人类癌症的约10-15%。参与ALT途径的肿瘤的特征在于存在单链5 '-C-富端粒突出端（C-突出端）。这种最近发现的ALT癌症标志将其与健康组织区分开来，并使C-突出端成为抗癌治疗的明确靶点。我们分析了来自人类和秀丽隐杆线虫（最近建立的ALT肿瘤的多细胞体内模型）的富含5 '-C和富含3'-G的端粒突出端的结构。结果表明，C.线虫和人类形成了根本不同的二级结构。C.线虫端粒DNA不仅与人类的端粒DNA不同，而且与其他多细胞真核生物的端粒DNA不同，这使我们能够鉴定端粒DNA的进化保守特性。在端粒DNA的结构组织的差异之间的C。秀丽线虫和人类对C. elegans作为ALT肿瘤模型。
There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10-15% of all human cancers. Tumours engaged in the ALT pathway are characterised by the presence of the single stranded 5'-C-rich telomeric overhang (C-overhang). This recently identified hallmark of ALT cancers distinguishes them from healthy tissues and renders the C-overhang as a clear target for anticancer therapy. We analysed structures of the 5'-C-rich and 3'-G-rich telomeric overhangs from human and Caenorhabditis elegans, the recently established multicellular in vivo model of ALT tumours. We show that the telomeric DNA from C. elegans and humans forms fundamentally different secondary structures. The unique structural characteristics of C. elegans telomeric DNA that are distinct not only from those of humans but also from those of other multicellular eukaryotes allowed us to identify evolutionarily conserved properties of telomeric DNA. Differences in structural organisation of the telomeric DNA between the C. elegans and human impose limitations on the use of the C. elegans as an ALT tumour model.