Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
Nucleic Acids Res. 2012 Aug;40(14):6649-59. doi: 10.1093/nar/gks358. Epub 2012 May 2.
Telomeres are transcribed into non-coding TElomeric Repeat containing RNAs (TERRA). We have employed a transcriptionally inducible telomere to investigate how telomere transcription affects telomere function in Saccharomyces cerevisiae. We report that telomere shortening resulting from high levels of telomere transcription stems from a DNA replication-dependent loss of telomere tracts, which can occur independent of both telomerase inhibition and homologous recombination. We show that in order for telomere loss to occur, transcription must pass through the telomere tract itself producing a TERRA molecule. We demonstrate that increased telomere transcription of a single telomere leads to a premature cellular senescence in the absence of a telomere maintenance mechanism (telomerase and homology directed repair). Similar rapid senescence and telomere shortening are also seen in sir2Δ cells with compromised telomere maintenance, where TERRA levels are increased at natural telomeres. These data suggest that telomere transcription must be tightly controlled to prevent telomere loss and early onset senescence.
端粒被转录为非编码的端粒重复序列 RNA（TERRA）。我们采用了一种转录诱导型端粒来研究端粒转录如何影响酿酒酵母中的端粒功能。我们报告说，高水平的端粒转录导致端粒缩短，这是由于 DNA 复制依赖性的端粒片段丢失所致，这种丢失可以独立于端粒酶抑制和同源重组发生。我们表明，为了发生端粒丢失，转录必须穿过端粒本身，产生 TERRA 分子。我们证明，在没有端粒维持机制（端粒酶和同源定向修复）的情况下，单个端粒的端粒转录增加会导致细胞过早衰老。在端粒维持受损的 sir2Δ 细胞中也观察到类似的快速衰老和端粒缩短，其中在天然端粒处 TERRA 水平增加。这些数据表明，端粒转录必须受到严格控制，以防止端粒丢失和早发性衰老。
