Trypanosoma brucei UMSBP2 is a single-stranded telomeric DNA binding protein essential for chromosome end protection.
Trypanosoma brucei UMSBP2 is a single-stranded telomeric DNA binding protein essential for chromosome end protection.
复制标题
DOI：
10.1093/nar/gky597
复制
发表时间：
2018-09-06
影响因子：
14.9
通讯作者：
Shlomai J
中科院分区：
文献类型：
--
作者：
Klebanov-Akopyan O;Mishra A;Glousker G;Tzfati Y;Shlomai J
通用微环序列结合蛋白（UMSBPs）是CCHC型锌指蛋白，它能结合富含G的单链序列UMS，该序列在线粒体（动基体）DNA的复制起点处保守存在。在此，我们报道布氏锥虫TbUMSBP2，此前被认为在线粒体DNA的复制和分离中起作用，它与细胞核中的端粒共定位，并且对端粒的结构、保护和功能至关重要。TbUMSBP2的敲低导致端粒聚集在一个或少数几个焦点，端粒附近的组蛋白H2A磷酸化，核分裂受损，核内再复制以及细胞生长停滞。此外，TbUMSBP2的缺失导致富含G的端粒突出端迅速减少，富含C的单链端粒DNA以及染色体外端粒环增加。这些结果表明TbUMSBP2对端粒的完整性和功能至关重要。线粒体UMS与端粒突出端之间的序列相似性以及UMSBPs能结合这两种序列的发现表明，在这两种细胞器的基因组复制和维持中，这些相互作用具有共同的起源和/或功能。在早期分化的原生生物中，核基因组和线粒体基因组从其祖先（可能是环状）基因组进化过程中，这一特征可能已经趋同或保留。
Universal minicircle sequence binding proteins (UMSBPs) are CCHC-type zinc-finger proteins that bind a single-stranded G-rich sequence, UMS, conserved at the replication origins of the mitochondrial (kinetoplast) DNA of trypanosomatids. Here, we report that Trypanosoma brucei TbUMSBP2, which has been previously proposed to function in the replication and segregation of the mitochondrial DNA, colocalizes with telomeres at the nucleus and is essential for their structure, protection and function. Knockdown of TbUMSBP2 resulted in telomere clustering in one or few foci, phosphorylation of histone H2A at the vicinity of the telomeres, impaired nuclear division, endoreduplication and cell growth arrest. Furthermore, TbUMSBP2 depletion caused rapid reduction in the G-rich telomeric overhang, and an increase in C-rich single-stranded telomeric DNA and in extrachromosomal telomeric circles. These results indicate that TbUMSBP2 is essential for the integrity and function of telomeres. The sequence similarity between the mitochondrial UMS and the telomeric overhang and the finding that UMSBPs bind both sequences suggest a common origin and/or function of these interactions in the replication and maintenance of the genomes in the two organelles. This feature could have converged or preserved during the evolution of the nuclear and mitochondrial genomes from their ancestral (likely circular) genome in early diverged protists.
登录
查看更多内容
影响因子：
5.4
作者：
Horn, David;McCulloch, Richard
通讯作者：
McCulloch, Richard
DOI：
10.1016/s0006-291x(03)01561-4
发表时间：
2003-09-12
影响因子：
3.1
作者：
Duhagon, MA;Dallagiovanna, B;Garat, B
通讯作者：
Garat, B
影响因子：
3.7
作者：
Field, Mark C.;Horn, David;Rout, Michael P.
通讯作者：
Rout, Michael P.
影响因子：
1.5
作者：
Glover, Lucy;Horn, David
通讯作者：
Horn, David
影响因子：
5.3
作者：
ABELIOVICH, H;TZFATI, Y;SHLOMAI, J
通讯作者：
SHLOMAI, J