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Mechanisms of transcription fidelity in prokaryotes and eukaryotes

Mechanisms of transcription fidelity in prokaryotes and eukaryotes
原核生物和真核生物的转录保真度机制
批准号:
9153672
负责人:
MIKHAIL KASHLEV
金额:
$74.31万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
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中文摘要
翻译
RNA聚合酶的转录延伸(RNAPs)在功能上与DNA的复制、修复和染色质组织有关,从而影响基因组的整体完整性和组织。结合启动后事件在调节mRNA合成中的中心作用,涉及RNAP的网络的复杂性表明,RNAP转录延伸率、保真度和经历转录停止的倾向的变化对细胞生理学具有广泛的影响。对转录保真度的生物学作用的分析将促进我们对RNAP底物特异性的理解。它将为临床上相关的NTP类似物的机制和副作用提供更多的见解。此外,转录保真度可能与转录偶联的DNA修复有关。具体地说,我们最近发现,酵母/哺乳动物Pol II识别DNA中的损伤的能力是由类似于调节同源NTP底物选择的机制决定的。这项研究的范围可能会扩大,以解决转录延伸和其他DNA交易之间的相互联系。
英文摘要
Transcription elongation by RNA polymerases (RNAPs) is functionally connected with DNA replication, repair, and chromatin organization, and thus affects the overall integrity and organization of the genome. Taken together with the central role of the post-initiation events in regulation of mRNA synthesis, the complexity of the network involving RNAP suggests that the changes in the transcription elongation rate, fidelity and the propensity of RNAP to undergo transcription arrest has a broad impact on cell physiology. The analyses of the biological role of transcription fidelity will promote our understanding of RNAP substrate specificity. It will provide additional insights into the mechanisms and side effects of the clinically relevant NTP analogues. In addition, transcription fidelity might be connected to the transcription-coupled DNA repair. Specifically, we have recently established that the ability of yeast/mammalian Pol II to recognize the lesion in the DNA is determined by the mechanisms similar to those regulating cognate NTP substrate selection. The scope of the research may be expanded to address the interconnection of transcription elongation and other DNA transactions.
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Transcription Through Nucleosomes by RNA Polymerase II
TRANSCRIPTION ELONGATION BY RNA POLYMERASE II
Basic Mechanism of Transcription Elongation by E. coli R
Transcription Through Nucleosomes in Vitro by E. coli RN
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