Tel1p preferentially associates with short telomeres to stimulate their elongation

Tel1p preferentially associates with short telomeres to stimulate their elongation
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DOI:
10.1016/j.molcel.2007.08.007
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发表时间:
2007-09-07
期刊:
影响因子:
16
通讯作者:
Runge, Kurt W.
Runge, Kurt W.
中科院分区:
生物学1区
文献类型:
--
作者:
Hector, Ronald E.;Shtofman, Rebecca L.;Runge, Kurt W.

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在许多生物体中,端粒DNA由长的短重复序列组成。较短的片段优先被端粒酶延长,这表明了一种保守的机制,可以识别和延长短的端粒。Tel1p是一种ATM家族检查点激酶,在端粒延长中起着重要作用,因为缺乏Tel1p的细胞具有短的端粒,并且显示端粒酶组分向端粒的募集减少。我们发现,Tel1p协会增加端粒缩短在体内端粒酶的存在或不存在下,Tel1p优先与最短的端粒。Tel1p协会是独立的Tel1p激酶活性和增强Mre11p。Tel1p过表达同时刺激端粒聚合酶介导的延长和Tel1p与所有端粒的关联。因此,Tel1p优先与最短的端粒相关联,并通过端粒酶刺激它们的延伸。
In many organisms, telomeric DNA consists of long tracts of short repeats. Shorter tracts are preferentially lengthened by telomerase, suggesting a conserved mechanism that recognizes and elongates short telomeres. Tel1p, an ATM family checkpoint kinase, plays an important role in telomere elongation, as cells lacking Tel1p have short telomeres and show reduced recruitment of telomerase components to telomeres. We show that Tel1p association increased as telomeres shortened in vivo in the presence or absence of telomerase and that Tel1p preferentially associated with the shortest telomeres. Tel1p association was independent of Tel1p kinase activity and enhanced by Mre11p. Tel1p overexpression simultaneously stimulated telomerase-mediated elongation and Tel1p association with all telomeres. Thus, Tel1p preferentially associates with the shortest telomeres and stimulates their elongation by telomerase.