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首页> 外文期刊>Biochemistry >Human CST Prefers G-Rich but Not Necessarily Telomeric Sequences
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Human CST Prefers G-Rich but Not Necessarily Telomeric Sequences

机译：人类CST更喜欢富含G，但不一定是端粒序列

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摘要

The human CST (CTC1-STN1-TEN1) heterotrimeric complex plays roles in both telomere maintenance and DNA replication through its ability to interact with single-stranded DNA (ssDNA) of a variety of sequences. The precise sequence specificity required to execute these functions is unknown. Telomere-binding proteins have been shown to specifically recognize key telomeric sequence motifs within ssDNA while accommodating nonspecifically recognized sequences through conformationally plastic interfaces. To better understand the role CST plays in these processes, we have produced a highly purified heterotrimer and elucidated the sequence requirements for CST recognition of ssDNA in vitro. CST discriminates against random sequence and binds a minimal ssDNA comprised of three repeats of telomeric sequence. Replacement of individual nucleotides with their complement reveals that guanines are specifically recognized in a largely additive fashion and that specificity is distributed uniformly throughout the ligand. Unexpectedly, adenosines are also well tolerated at these sites, but cytosines are disfavored. Furthermore, sequences unrelated to the telomere repeat, yet still G-rich, bind CST well. Thus, CST is not inherently telomere-specific, but rather is a G-rich sequence binder. This biochemical activity is reminiscent of the yeast t-RPA and Tetrahymena thermophila CST complexes and is consistent with roles at G-rich sites throughout the genome.
机译：通过其与各种序列的单链DNA（SSDNA）相互作用的能力，人CST（CTC1-STN1-TEN1）异映型复合物在端粒维持和DNA复制中起作用。执行这些函数所需的精确序列特异性是未知的。已经证明了端粒结合蛋白在通过构象塑料界面容纳非特异性识别的序列的同时具体识别SSDNA内的关键端粒序列基序。为了更好地理解CST在这些过程中的作用，我们产生了高度纯化的异映体，并阐明了体外SSDNA的CST识别的序列要求。 CST鉴别随机序列并结合包含三种端粒序列的三种重复的最小SSDNA。用它们的补体替换个体核苷酸表明，偶胆脉以很大程度的添加方式特异性地识别，并且该特异性在整个配体中均匀地分布。出乎意料地，腺苷在这些位点也耐受良好，但胞嘧啶是不歧视的。此外，与端粒重复不相关的序列，但尚不富有G，结合CST井。因此，CST不是固有的端粒特异性，而是富含G的序列粘合剂。这种生化活性是让酵母T-RPA和四环素热榈菌CST复合物中康复，并与整个基因组的富含G的位点一致。

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  • 来源
    《Biochemistry》 |2017年第32期|共9页
  • 作者

    Hom Robert A.; Wuttke Deborah S.;

  • 作者单位

    Univ Colorado Dept Chem &

    Biochem UCB 596 Boulder CO 80309 USA;

    Univ Colorado Dept Chem &

    Biochem UCB 596 Boulder CO 80309 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
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