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首页> 外文期刊>PLoS Genetics >Epigenetic Telomere Protection by Drosophila DNA Damage Response Pathways
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Epigenetic Telomere Protection by Drosophila DNA Damage Response Pathways

机译：果蝇DNA损伤反应途径的表观遗传端粒保护。

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Analysis of terminal deletion chromosomes indicates that a sequence-independent mechanism regulates protection of Drosophila telomeres. Mutations in Drosophila DNA damage response genes such as atm/tefu, mre11, or rad50 disrupt telomere protection and localization of the telomere-associated proteins HP1 and HOAP, suggesting that recognition of chromosome ends contributes to telomere protection. However, the partial telomere protection phenotype of these mutations limits the ability to test if they act in the epigenetic telomere protection mechanism. We examined the roles of the Drosophila atm and atr-atrip DNA damage response pathways and the nbs homolog in DNA damage responses and telomere protection. As in other organisms, the atm and atr-atrip pathways act in parallel to promote telomere protection. Cells lacking both pathways exhibit severe defects in telomere protection and fail to localize the protection protein HOAP to telomeres. Drosophila nbs is required for both atm- and atr-dependent DNA damage responses and acts in these pathways during DNA repair. The telomere fusion phenotype of nbs is consistent with defects in each of these activities. Cells defective in both the atm and atr pathways were used to examine if DNA damage response pathways regulate telomere protection without affecting telomere specific sequences. In these cells, chromosome fusion sites retain telomere-specific sequences, demonstrating that loss of these sequences is not responsible for loss of protection. Furthermore, terminally deleted chromosomes also fuse in these cells, directly implicating DNA damage response pathways in the epigenetic protection of telomeres. We propose that recognition of chromosome ends and recruitment of HP1 and HOAP by DNA damage response proteins is essential for the epigenetic protection of Drosophila telomeres. Given the conserved roles of DNA damage response proteins in telomere function, related mechanisms may act at the telomeres of other organisms.
机译：末端缺失染色体的分析表明，序列独立的机制调节果蝇端粒的保护。果蝇DNA损伤应答基因（如atm / tefu，mre11或rad50）中的突变破坏了端粒保护，并端粒相关蛋白HP1和HOAP定位，这表明染色体末端的识别有助于端粒保护。但是，这些突变的部分端粒保护表型限制了测试它们是否在表观遗传端粒保护机制中起作用的能力。我们检查了果蝇atm和atr-atrip DNA损伤反应途径和nbs同源物在DNA损伤反应和端粒保护中的作用。与其他生物一样，atm和atr-atrip通路同时发挥作用，促进端粒保护。缺少这两种途径的细胞在端粒保护中表现出严重缺陷，并且无法将保护蛋白HOAP定位于端粒。果蝇nbs是atm和atr依赖性DNA损伤反应所必需的，并在DNA修复过程中以这些途径起作用。 nbs的端粒融合表型与这些活动中的每一个的缺陷一致。 atm和atr途径均存在缺陷的细胞用于检查DNA损伤应答途径是否在不影响端粒特异性序列的情况下调节端粒保护。在这些细胞中，染色体融合位点保留了端粒特异的序列，表明这些序列的丢失与保护作用的丧失无关。此外，末端缺失的染色体也融合在这些细胞中，直接牵涉端粒的表观遗传学保护中的DNA损伤反应途径。我们提出，DNA损伤反应蛋白对染色体末端的识别和HP1和HOAP的募集对于果蝇端粒的表观遗传学保护至关重要。鉴于DNA损伤反应蛋白在端粒功能中的保守作用，相关机制可能作用于其他生物的端粒。

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