Telomere length dynamics in response to DNA damage in malaria parasites.

Telomere length dynamics in response to DNA damage in malaria parasites.
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疟疾寄生虫DNA损伤后的端粒长度动态变化。

DOI:
10.1016/j.isci.2021.102082
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发表时间:
2021-02-19
期刊:
影响因子:
5.8
通讯作者:
Deitsch KW
Deitsch KW
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Reed J;Kirkman LA;Kafsack BF;Mason CE;Deitsch KW

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疟疾仍然是发展中世界发病率和死亡率的主要原因。最近的工作涉及染色体末端稳定性和DNA修复突破端粒愈合作为变体抗原多样化的有力驱动因素,从而将维持基因组完整性的基本机制与宿主-寄生虫相互作用的各个方面联系起来。在这里,我们应用长读测序技术,精确地检查端粒添加和染色体末端稳定化的动态响应于亚端粒区域内的双链断裂。我们观察到,端粒愈合的过程中诱导的端粒重复序列的初始合成以及超过所需的最低数量的末端稳定性。然而,一旦稳定下来,这些新产生的端粒似乎功能正常,最终恢复到接近完整染色体末端的长度。这些结果与最近在人类身上的观察结果相似,表明染色体末端修复存在进化上保守的机制。疟疾寄生虫的亚端粒结构域包含毒力基因暴露于DNA损伤导致端粒长度在全基因组范围内增加断裂的染色体末端经历端粒愈合,延长其长度在愈合的端粒处延长的重复序列数量随着时间的推移而减少天体生物学;染色体组织;组学;寄生虫学
Malaria remains a major cause of morbidity and mortality in the developing world. Recent work has implicated chromosome end stability and the repair of DNA breaks through telomere healing as potent drivers of variant antigen diversification, thus associating basic mechanisms for maintaining genome integrity with aspects of host-parasite interactions. Here we applied long-read sequencing technology to precisely examine the dynamics of telomere addition and chromosome end stabilization in response to double-strand breaks within subtelomeric regions. We observed that the process of telomere healing induces the initial synthesis of telomere repeats well in excess of the minimal number required for end stability. However, once stabilized, these newly created telomeres appear to function normally, eventually returning to a length nearing that of intact chromosome ends. These results parallel recent observations in humans, suggesting an evolutionarily conserved mechanism for chromosome end repair. Subtelomeric domains of malaria parasites contain virulence genes Exposure to DNA damage causes a genome-wide increase in telomere lengths Broken chromosome ends undergo telomere healing, extending their length The extended number of repeats at healed telomeres lessens over time Astrobiology; chromosome organization; omics; parasitology
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