POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.
POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.
复制标题
DOI：
10.1093/nar/gkac023
复制
发表时间：
2022-02-28
影响因子：
14.9
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Rabbani MAG;Tonini ML;Afrin M;Li B
布鲁氏锥虫引起人类非洲锥虫病，并依次表达不同的VSGs，其主要表面抗原，以实现宿主免疫逃避。VSG由亚端粒基因座单等位表达，端粒蛋白调控VSG单等位基因表达和VSG切换。布鲁氏菌端粒酶对端粒维持至关重要，但尚未发现端粒酶的调节因子。布鲁氏体似乎缺乏OB折叠端粒特异性ssDNA结合因子，这是协调高级真核生物端粒G链和c链合成的关键。我们确定POLIE是端粒完整性所必需的端粒蛋白。pole缺失的细胞具有更频繁的VSG基因转换介导的VSG开关和端粒环（t -环）数量的增加，表明pole抑制端粒/亚端粒的DNA重组。pole耗竭显著延长了端粒3 '的悬垂，这表明pole对于协调两个端粒链的DNA合成是必不可少的。POLIE缺失增加端粒酶依赖的端粒g链延伸水平，确定POLIE是第一个抑制端粒酶的布鲁氏T.端粒蛋白。此外，POLIE的消耗导致端粒c环水平升高，表明端粒c链经历了复制压力，POLIE可能促进了端粒c链的合成。因此，布鲁氏体利用一种新的机制来协调端粒G链和c链DNA的合成。
Trypanosoma brucei causes human African trypanosomiasis and sequentially expresses distinct VSGs, its major surface antigen, to achieve host immune evasion. VSGs are monoallelically expressed from subtelomeric loci, and telomere proteins regulate VSG monoallelic expression and VSG switching. T. brucei telomerase is essential for telomere maintenance, but no regulators of telomerase have been identified. T. brucei appears to lack OB fold-containing telomere-specific ssDNA binding factors that are critical for coordinating telomere G- and C-strand syntheses in higher eukaryotes. We identify POLIE as a telomere protein essential for telomere integrity. POLIE-depleted cells have more frequent VSG gene conversion-mediated VSG switching and an increased amount of telomeric circles (T-circles), indicating that POLIE suppresses DNA recombination at the telomere/subtelomere. POLIE-depletion elongates telomere 3′ overhangs dramatically, indicating that POLIE is essential for coordinating DNA syntheses of the two telomere strands. POLIE depletion increases the level of telomerase-dependent telomere G-strand extension, identifying POLIE as the first T. brucei telomere protein that suppresses telomerase. Furthermore, depletion of POLIE results in an elevated telomeric C-circle level, suggesting that the telomere C-strand experiences replication stress and that POLIE may promote telomere C-strand synthesis. Therefore, T. brucei uses a novel mechanism to coordinate the telomere G- and C-strand DNA syntheses.
登录
查看更多内容
影响因子：
64.8
作者：
Chen, Liuh-Yow;Redon, Sophie;Lingner, Joachim
通讯作者：
Lingner, Joachim
DOI：
10.1073/pnas.1600344113
发表时间：
2016-06-28
影响因子：
11.1
作者：
Glover, Lucy;Hutchinson, Sebastian;Horn, David
通讯作者：
Horn, David
影响因子：
10.5
作者：
Arnoult, Nausica;Saintome, Carole;Londono-Vallejo, Arturo
通讯作者：
Londono-Vallejo, Arturo
影响因子：
1.5
作者：
Glover, Lucy;Horn, David
通讯作者：
Horn, David
影响因子：
64.8
作者：
DELANGE, T;BORST, P
通讯作者：
BORST, P