Telomerase core components protect Candida telomeres from aberrant overhang accumulation
Telomerase core components protect Candida telomeres from aberrant overhang accumulation
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DOI：
10.1073/pnas.0700327104
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发表时间：
2007-07-10
影响因子：
11.1
通讯作者：
Lue, Neal F.
中科院分区：
文献类型：
--
作者：
Hsu, Min;McEachern, Michael J.;Lue, Neal F.
端粒酶是一种细胞逆转录酶，其延伸端粒末端重复序列的一条链（G链）。除了在端粒长度维持中的这种作用之外，端粒酶已经被提出在染色体末端起保护作用，尽管这在机理上还没有很好地理解。早期的分析表明，在致病性酵母菌白色念珠菌中，端粒酶催化逆转录酶亚基（TERT/EST 2）可以保护端粒免受溶核降解。在这份报告中，我们证明了RNA组分（TER 1）具有类似的功能，除了完全丧失端粒酶活性和进行性端粒磨损，ter 1-AA菌株表现出显着增加的量的G-链突出，与异常降解的互补C-链。我们还表明，催化不称职的EST 2蛋白可以抑制这种突出端的积累在est 2-Delta Delta突变体的野生型蛋白质相同的程度。总而言之，我们的数据支持念珠菌端粒酶核心成分通过独立于其催化活性的机制介导保护功能的观点。
Telomerase is a cellular reverse transcriptase that extends one strand (the G-strand) of the telomere terminal repeats. Aside from this role in telomere length maintenance, telomerase has been proposed to serve a protective function at chromosome ends, although this is not well understood mechanistically. Earlier analysis suggests that, in the pathogenic yeast Candida albicans, the catalytic reverse transcriptase subunit of telomerase (TERT/EST2) can protect telomeres against nucleolytic degradation. In this report we demonstrate that the RNA component (TER1) has a similar function; in addition to complete loss of telomerase activity and progressive telomere attrition, the ter1-AA strains manifested a dramatic increase in the amount of G-strand overhangs, consistent with aberrant degradation of the complementary C-strand. We also demonstrate that a catalytically incompetent EST2 protein can suppress such overhang accumulation in the est2-Delta Delta mutant to the same extent as the wild-type protein. Altogether, our data support the notion that the Candida telomerase core components mediate a protective function through a mechanism that is independent of its catalytic activity.