Transcript-assisted transcriptional proofreading
Transcript-assisted transcriptional proofreading
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DOI：
10.1126/science.1127422
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发表时间：
2006-07-28
期刊：
影响因子：
56.9
通讯作者：
Severinov, Konstantin
中科院分区：
文献类型：
--
作者：
Zenkin, Nikolay;Yuzenkova, Yulia;Severinov, Konstantin
模板依赖性核酸合成的保真度是稳定遗传和无错误基因表达的主要决定因素。通过DNA依赖性RNA聚合酶（RNAP）确保转录保真度的机制（或多个机制）尚未完全理解。在这里，我们表明，3'端近端核苷酸的新生转录刺激水解的倒数第二个磷酸二酯键提供活性基团和协调键的RNAP活性中心。这种刺激在错误掺入核苷酸的情况下高得多。我们发现，在转录延伸，水解反应刺激的错误掺入的核苷酸校对大多数的错误掺入事件，从而作为一个内在的机制，转录保真度。
Fidelity of template-dependent nucleic acid synthesis is the main determinant of stable heredity and error-free gene expression. The mechanism ( or mechanisms) ensuring fidelity of transcription by DNA-dependent RNA polymerases (RNAPs) is not fully understood. Here, we show that the 3' end - proximal nucleotide of the nascent transcript stimulates hydrolysis of the penultimate phosphodiester bond by providing active groups and coordination bonds to the RNAP active center. This stimulation is much higher in the case of misincorporated nucleotide. We show that during transcription elongation, the hydrolytic reaction stimulated by misincorporated nucleotides proofreads most of the misincorporation events and thus serves as an intrinsic mechanism of transcription fidelity.