Telomere maintenance in African trypanosomes.
Telomere maintenance in African trypanosomes.
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DOI：
10.3389/fmolb.2023.1302557
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
端粒的维持对于携带线性染色体的真核细胞中的基因组完整性和染色体稳定性是必不可少的，因为端粒形成专门的结构以掩蔽天然染色体末端免受DNA损伤修复机制的影响并防止端粒DNA的溶核降解。在布氏锥虫和其他几种微生物病原体中，参与抗原变异（宿主免疫逃避和长期感染所必需的关键致病机制）的毒力基因位于亚端粒，这些主要表面抗原的表达和转换受端粒蛋白和端粒结构的调节。因此，了解端粒维持机制以及这些病原体如何在端粒/亚端粒的稳定性和可塑性之间实现平衡，将有助于开发更好的方法来根除这些病原体引起的人类疾病。端粒复制面临着几个挑战，“末端复制问题”是一个关键的障碍，可以导致增殖细胞中的端粒进行性缩短。为了克服这一挑战，大多数真核生物使用端粒酶来延长富含G的端粒链。此外，许多端粒蛋白使用复杂的机制来协调端粒酶介导的端粒G链从头合成和端粒C链填充，这在哺乳动物细胞中已被广泛研究。然而，我们最近发现锥虫缺乏许多在其哺乳动物宿主中鉴定的端粒蛋白，这些蛋白对端粒末端加工至关重要。相反，T。布氏杆菌使用一种独特的DNA聚合酶，PolIE，它属于DNA聚合酶A家族（E. coli DNA PolI家族），以协调端粒G-和C-链合成。在这篇综述中，我将首先简要总结目前的理解端粒末端加工在哺乳动物。随后，我将描述PolIE介导的T染色体端粒G链和C链合成的协调。布氏杆菌和这一最新发现的含义。
Telomere maintenance is essential for genome integrity and chromosome stability in eukaryotic cells harboring linear chromosomes, as telomere forms a specialized structure to mask the natural chromosome ends from DNA damage repair machineries and to prevent nucleolytic degradation of the telomeric DNA. In Trypanosoma brucei and several other microbial pathogens, virulence genes involved in antigenic variation, a key pathogenesis mechanism essential for host immune evasion and long-term infections, are located at subtelomeres, and expression and switching of these major surface antigens are regulated by telomere proteins and the telomere structure. Therefore, understanding telomere maintenance mechanisms and how these pathogens achieve a balance between stability and plasticity at telomere/subtelomere will help develop better means to eradicate human diseases caused by these pathogens. Telomere replication faces several challenges, and the “end replication problem” is a key obstacle that can cause progressive telomere shortening in proliferating cells. To overcome this challenge, most eukaryotes use telomerase to extend the G-rich telomere strand. In addition, a number of telomere proteins use sophisticated mechanisms to coordinate the telomerase-mediated de novo telomere G-strand synthesis and the telomere C-strand fill-in, which has been extensively studied in mammalian cells. However, we recently discovered that trypanosomes lack many telomere proteins identified in its mammalian host that are critical for telomere end processing. Rather, T. brucei uses a unique DNA polymerase, PolIE that belongs to the DNA polymerase A family (E. coli DNA PolI family), to coordinate the telomere G- and C-strand syntheses. In this review, I will first briefly summarize current understanding of telomere end processing in mammals. Subsequently, I will describe PolIE-mediated coordination of telomere G- and C-strand synthesis in T. brucei and implication of this recent discovery.
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