Telomere capping and cellular checkpoints: clues from fruit flies
Telomere capping and cellular checkpoints: clues from fruit flies
复制标题
DOI：
10.1159/000167824
复制
发表时间：
2008-01-01
影响因子：
1.7
通讯作者：
Cenci, G.
中科院分区：
文献类型：
--
作者：
Ciapponi, L.;Cenci, G.
在大多数生物体中，端粒由重复的富含G的序列组成，这些序列被特定的逆转录酶端粒酶延长。大量的蛋白质被这些末端重复序列招募，形成调节端粒酶活性和保护端粒免于降解和重组的专门结构。果蝇缺乏端粒酶，端粒长度通过三个专门的反转录转座子的转座来维持。此外，与酵母和哺乳动物不同，果蝇端粒是表观遗传决定的，不依赖于序列的结构。然而，果蝇端粒行为所需的几种蛋白质在进化上是保守的。这些包括Mre 11-Rad 50-Nbs（MRN）复合物和共济失调毛细血管扩张突变（ATM）激酶，这是防止端粒融合所必需的。此外，最近的研究提供了证据表明，果蝇未加帽的端粒引起DNA损伤反应（DDR），就像功能失调的酵母和人类端粒一样。未加帽的果蝇端粒也通过募集SAC激酶BubR 1来激活纺锤体组装检查点（SAC）。端粒诱导的DDR和SAC都需要MRN复合物的野生型功能。此外，虽然DDR由ATR激酶介导，但SAC激活需要ATM和ATR活性。这些结果表明，DNA修复系统在果蝇端粒中起着多重作用，突出了这种模式生物的重要性，为研究DNA修复和端粒维持之间的关系。版权所有（C）2008 S. Karger AG，巴塞尔
In most organisms, telomeres consist of repetitive G-rich sequences that are elongated by a specific reverse transcriptase, telomerase. A large number of proteins are recruited by these terminal repeats, forming specialized structures that regulate telomerase activity and protect telomeres from degradation and recombination. Drosophila lacks telomerase and telomere length is maintained by transposition of three specialized retrotransposons. In addition, unlike yeast and mammals, Drosophila telomeres are epigenetically determined, sequence-independent structures. However, several proteins required for Drosophila telomere behavior are evolutionarily conserved. These include the Mre11-Rad50-Nbs (MRN) complex and the Ataxia Telangiectasia Mutated (ATM) kinase, which are required to prevent telomeric fusions. In addition, recent studies have provided evidence that Drosophila uncapped telomeres elicit a DNA damage response (DDR) just as dysfunctional yeast and human telomeres. Uncapped Drosophila telomeres also activate the spindle assembly checkpoint ( SAC) by recruiting the SAC kinase BubR1. Telomere-induced DDR and SAC both require the wild type function of the MRN complex. In addition, while DDR is mediated by ATR kinase, SAC activation requires both the ATM and ATR activities. These results indicate that the DNA repair systems play multiple roles at Drosophila telomeres, highlighting the importance of this model organism for investigations on the relationships between DNA repair and telomere maintenance. Copyright (C) 2008 S. Karger AG, Basel