Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma Roma, Italy ; Dipartimento di Biologia e Biotecnologie "C. Darwin," Sapienza Università di Roma Roma, Italy.
Front Oncol. 2013 May 10;3:112. doi: 10.3389/fonc.2013.00112. eCollection 2013.
Drosophila lacks telomerase and fly telomeres are elongated by occasional transposition of three specialized retroelements. Drosophila telomeres do not terminate with GC-rich repeats and are assembled independently of the sequence of chromosome ends. Recent work has shown that Drosophila telomeres are capped by the terminin complex, which includes the fast-evolving proteins HOAP, HipHop, Moi, and Ver. These proteins, which are not conserved outside Drosophilidae and closely related Diptera, localize and function exclusively at telomeres, protecting them from fusion events. Other proteins required to prevent end-to-end fusion in flies include HP1, Eff/UbcD1, ATM, the components of the Mre11-Rad50-Nbs (MRN) complex, and the Woc transcription factor. These proteins do not share the terminin properties; they are evolutionarily conserved non-fast-evolving proteins that do not accumulate only at telomeres and do not serve telomere-specific functions. We propose that following telomerase loss, Drosophila rapidly evolved terminin to bind chromosome ends in a sequence-independent manner. This hypothesis suggests that terminin is the functional analog of the shelterin complex that protects human telomeres. The non-terminin proteins are instead likely to correspond to ancestral telomere-associated proteins that did not evolve as rapidly as terminin because of the functional constraints imposed by their involvement in diverse cellular processes. Thus, it appears that the main difference between Drosophila and human telomeres is in the protective complexes that specifically associate with the DNA termini. We believe that Drosophila telomeres offer excellent opportunities for investigations on human telomere biology. The identification of additional Drosophila genes encoding non-terminin proteins involved in telomere protection might lead to the discovery of novel components of human telomeres.
果蝇缺乏端粒酶，其端粒通过三个特殊的反转录元件偶尔易位而延长。果蝇的端粒不以富含 GC 的重复序列结尾，并且其组装与染色体末端的序列无关。最近的研究表明，果蝇的端粒由端粒复合物所覆盖，其中包括快速进化的蛋白 HOAP、HipHop、Moi 和 Ver。这些蛋白在果蝇科和密切相关的双翅目之外没有保守性，仅在端粒处定位并发挥功能，保护它们免受融合事件的影响。其他防止果蝇末端融合所必需的蛋白包括 HP1、Eff/UbcD1、ATM、Mre11-Rad50-Nbs（MRN）复合物的组成部分和 Woc 转录因子。这些蛋白不具有端粒复合物的特性；它们是进化保守的非快速进化蛋白，不仅在端粒处积累，而且不具有端粒特异性功能。我们提出，在端粒酶丢失后，果蝇迅速进化出端粒复合物，以非序列依赖的方式结合染色体末端。这个假说表明，端粒复合物是保护人类端粒的 shelterin 复合物的功能类似物。而非端粒复合物的蛋白可能对应于祖先的端粒相关蛋白，由于它们参与多种细胞过程，因此没有像端粒复合物那样快速进化。因此，果蝇和人类端粒之间的主要区别似乎在于与 DNA 末端特异性结合的保护复合物。我们认为，果蝇端粒为研究人类端粒生物学提供了极好的机会。鉴定参与端粒保护的额外的果蝇编码非端粒复合物的基因可能会发现人类端粒的新成分。
