PDF(Pubmed)
Abstract：
Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries and block nucleolytic degradation of the natural chromosome ends, although the detailed underlying mechanisms are not identical. In addition, the specialized telomere structure exerts a repressive epigenetic effect on expression of genes located at subtelomeres in a number of eukaryotic organisms. This so-called telomeric silencing also affects virulence of a number of microbial pathogens that undergo antigenic variation/phenotypic switching. Telomere proteins, particularly the RAP1 homologs, have been shown to be a key player for telomeric silencing. RAP1 homologs also suppress the expression of Telomere Repeat-containing RNA (TERRA), which is linked to their roles in telomere stability maintenance. The functions of RAP1s in suppressing telomere recombination are largely conserved from kinetoplastids to mammals. However, the underlying mechanisms of RAP1-mediated telomeric silencing have many species-specific features. In this review, I will focus on Trypanosoma brucei RAP1\'s functions in suppressing telomeric/subtelomeric DNA recombination and in the regulation of monoallelic expression of subtelomere-located major surface antigen genes. Common and unique mechanisms will be compared among RAP1 homologs, and their implications will be discussed.
摘要：
虽然位于染色体末端,端粒是一种重要的染色体成分，有助于维持从原生动物到哺乳动物的基因组完整性和染色体稳定性。端粒蛋白在染色体末端保护中的作用是保守的,它们抑制各种DNA损伤反应机制并阻止天然染色体末端的核解降解，尽管详细的潜在机制并不相同。此外,在许多真核生物中，特殊的端粒结构对位于端粒下的基因表达具有抑制作用。这种所谓的端粒沉默也影响许多经历抗原变异/表型转换的微生物病原体的毒力。端粒蛋白,特别是RAP1同源物，已被证明是端粒沉默的关键参与者。RAP1同源物还抑制端粒重复序列RNA（TERRA）的表达，这与它们在端粒稳定性维持中的作用有关。从动体到哺乳动物，RAP1s在抑制端粒重组中的功能在很大程度上是保守的。然而,RAP1介导的端粒沉默的潜在机制具有许多物种特异性特征.在这次审查中,我将重点介绍布鲁氏锥虫RAP1在抑制端粒/亚端粒DNA重组和调节位于端粒下的主要表面抗原基因的单等位基因表达方面的功能。将在RAP1同源物之间比较常见和独特的机制，它们的含义将被讨论。
