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: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9153672
• 关键词: Address; Adverse effects; Affect; Biological; Cell physiology; Cells; Chromatin; Coupled; DNA; DNA Damage; DNA Polymerase II; DNA Repair; DNA biosynthesis; DNA-Directed RNA Polymerase; Detection; Development; Eukaryota; Event; Genetic Transcription; Genome; Goals; Growth; Lesion; Life; Messenger RNA; Methods; Prokaryotic Cells; Protein Analysis; RNA Splicing; Regulation; Research; Role; Substrate Specificity; Transcription Elongation; Yeasts; analog; clinically relevant; insight; repaired; transcriptome sequencing

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.

RNA聚合酶（RNAPs）的转录延伸在功能上与DNA复制、修复和染色质组织相关，从而影响基因组的整体完整性和组织。两者结合的核心作用的启动后事件在mRNA合成的调节，涉及RNAP的网络的复杂性表明，在转录延伸率，保真度和倾向的RNAP进行转录停滞的变化有广泛的影响细胞生理学。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。它将为临床相关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DNA修复有关。具体来说，我们最近已经确定，酵母/哺乳动物Pol II识别DNA中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。研究的范围可能会扩大到解决转录延伸和其他DNA交易的相互联系。