Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops.

Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops.
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DOI:
10.1093/nar/gkw779
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发表时间:
2016-11-02
影响因子:
14.9
通讯作者:
Griffith JD
Griffith JD
中科院分区:
生物学2区
文献类型:
--
作者:
Kar A;Willcox S;Griffith JD

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染色体末端DNA环的形成(t环)和端粒转录产生富g RNA (TERRA)是端粒的两个主要特征。为了探索它们之间可能的联系,我们使用了人工的人类端粒,其中包含T7或T3启动子两侧的TTAGGG重复序列长阵列。这些dna的转录在单个分子内产生高频率的t环,并在不同dna的端粒序列上产生同源重组事件。t型环的形成不需要单链悬垂,这是因为两个末端链都插入到前面的双链中。这些环非常稳定,一些抗RNase H的TERRA留在t环上,可能增加了它们的稳定性。含有TTAGTG或TGAGTG重复序列的dna转录显示环路形成大大减少。虽然在细胞中可能有多种途径导致t环的形成,但这里揭示的途径并不依赖于庇护层,而是依赖于端粒DNA打开转录时的独特特征。因此,端粒序列的进化可能促进了它们自我循环的能力。
The formation of DNA loops at chromosome ends (t-loops) and the transcription of telomeres producing G-rich RNA (TERRA) represent two central features of telomeres. To explore a possible link between them we employed artificial human telomeres containing long arrays of TTAGGG repeats flanked by the T7 or T3 promoters. Transcription of these DNAs generates a high frequency of t-loops within individual molecules and homologous recombination events between different DNAs at their telomeric sequences. T-loop formation does not require a single strand overhang, arguing that both terminal strands insert into the preceding duplex. The loops are very stable and some RNase H resistant TERRA remains at the t-loop, likely adding to their stability. Transcription of DNAs containing TTAGTG or TGAGTG repeats showed greatly reduced loop formation. While in the cell multiple pathways may lead to t-loop formation, the pathway revealed here does not depend on the shelterins but rather on the unique character of telomeric DNA when it is opened for transcription. Hence, telomeric sequences may have evolved to facilitate their ability to loop back on themselves.
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