Reed Jake, Kirkman Laura A, Kafsack Björn F, Mason Christopher E, Deitsch Kirk W
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.
Department of Internal Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA.
iScience. 2021 Jan 20;24(2):102082. doi: 10.1016/j.isci.2021.102082. eCollection 2021 Feb 19.
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.
疟疾仍然是发展中世界发病和死亡的主要原因。最近的研究表明，染色体末端稳定性以及通过端粒修复来修复DNA断裂是变异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，我们应用长读长测序技术来精确研究端粒添加和染色体末端稳定在亚端粒区域双链断裂响应中的动态变化。我们观察到，端粒修复过程会诱导端粒重复序列的初始合成，远远超过末端稳定所需的最小数量。然而，一旦稳定下来，这些新形成的端粒似乎能正常发挥功能，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中的观察结果相似，表明存在一种进化上保守的染色体末端修复机制。
