Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi
Repetitive DNA is associated with centromeric domains in Trypanosoma brucei but not Trypanosoma cruzi
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DOI：
10.1186/gb-2007-8-3-r37
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发表时间：
2007-01-01
期刊：
影响因子：
12.3
通讯作者：
Kelly, John M.
中科院分区：
文献类型：
--
作者：
Obado, Samson O.;Bot, Christopher;Kelly, John M.
背景：锥虫是一种从真核生物分支出来的寄生原虫。他们的基因组显示几个不寻常的特点，尽管完成了锥虫基因组计划，着丝粒DNA的位置尚未identified.Results：我们报告的证据，在克氏锥虫和布氏锥虫的着丝粒DNA的位置和性质。于T. cruzi等人，我们使用端粒相关的染色体片段化，发现主要由简并逆转录转座子组成的富含GC的转录“链开关”结构域是赋予有丝分裂稳定性的区域的共同特征。与此一致，依托泊苷介导的拓扑异构酶-II裂解，活性着丝粒的生化标记，集中在这些领域。在T.在布氏杆菌中，拓扑异构酶II活性也集中在包含含有转座因子的定向基因簇之间的区域的单个基因座。与T. cruzi，然而，这些基因座也含有延伸超过几个DNA酶的富含AT的重复序列的阵列。拓扑异构酶-Ⅱ在T. brucei 1号染色体和T. cruzi 3号染色体是同线的，表明着丝粒位置已经保守了2亿多年。霸王布氏中间体和微小染色体，其中缺乏管家基因，不表现出特定位点的积累拓扑异构酶-II，这表明这些非典型染色体的分离可能涉及一个着丝粒独立mechanism.Conclusion：在锥虫着丝粒DNA的本地化填补了一个重大空白，我们在这些重要的人类病原体的基因组组织的理解。这些数据是一个重要的一步，确定和功能特性的其他决定因素的着丝粒功能，并提供了一个框架，解剖染色体分离的机制。
Background: Trypanosomes are parasitic protozoa that diverged early from the main eukaryotic lineage. Their genomes display several unusual characteristics and, despite completion of the trypanosome genome projects, the location of centromeric DNA has not been identified.Results: We report evidence on the location and nature of centromeric DNA in Trypanosoma cruzi and Trypanosoma brucei. In T. cruzi, we used telomere-associated chromosome fragmentation and found that GC-rich transcriptional 'strand-switch' domains composed predominantly of degenerate retrotranposons are a shared feature of regions that confer mitotic stability. Consistent with this, etoposide-mediated topoisomerase-II cleavage, a biochemical marker for active centromeres, is concentrated at these domains. In the 'megabase-sized' chromosomes of T. brucei, topoisomerase II activity is also focused at single loci that encompass regions between directional gene clusters that contain transposable elements. Unlike T. cruzi, however, these loci also contain arrays of AT-rich repeats stretching over several kilobases. The sites of topoisomerase-II activity on T. brucei chromosome 1 and T. cruzi chromosome 3 are syntenic, suggesting that centromere location has been conserved for more than 200 million years. The T. brucei intermediate and minichromosomes, which lack housekeeping genes, do not exhibit site-specific accumulation of topoisomerase-II, suggesting that segregation of these atypical chromosomes might involve a centromereindependent mechanism.Conclusion: The localization of centromeric DNA in trypanosomes fills a major gap in our understanding of genome organization in these important human pathogens. These data are a significant step towards identifying and functionally characterizing other determinants of centromere function and provide a framework for dissecting the mechanisms of chromosome segregation.