RNA polymerase fidelity and transcriptional proofreading

RNA polymerase fidelity and transcriptional proofreading
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DOI:
10.1016/j.sbi.2009.10.009
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发表时间:
2009-12-01
影响因子:
6.8
通讯作者:
Cramer, Patrick
Cramer, Patrick
中科院分区:
生物学2区
文献类型:
--
作者:
Sydow, Jasmin F.;Cramer, Patrick

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虽然DNA聚合酶(DNAP)的保真度机制已经被详细研究,但RNA聚合酶(RNAP)的保真度机制仍然知之甚少。新的功能和结构研究现在表明,RNAP如何选择正确的核苷三磷酸(NTP)底物以防止转录错误,以及酶如何在校对过程中检测和移除错误结合的核苷酸。校对始于将错误结合的核苷酸从DNA模板上剥离,从而暂停转录。随后RNAP的一个位置的后续回溯使得能够对包含错误结合的核苷酸的RNA二核苷酸进行核裂解。由于切割发生在用于聚合的同一活性部位,RNAP的校对机制不同于DNAP,后者包含不同的核酸酶特异性活性部位。
Whereas mechanisms underlying the fidelity of DNA polymerases (DNAPs) have been investigated in detail, RNA polymerase (RNAP) fidelity mechanisms remained poorly understood. New functional and structural studies now suggest how RNAPs select the correct nucleoside triphosphate (NTP) substrate to prevent transcription errors, and how the enzymes detect and remove a misincorporated nucleotide during proofreading. Proofreading begins with fraying of the misincorporated nucleotide away from the DNA template, which pauses transcription. Subsequent backtracking of RNAP by one position enables nucleolytic cleavage of an RNA dinucleotide that contains the misincorporated nucleotide. Since cleavage occurs at the same active site that is used for polymerization, the RNAP proofreading mechanism differs from that used by DNAPs, which contain a distinct nuclease specific active site.