Mechanism of transcription modulation by the transcription-repair coupling factor

被引：7

作者：

Paudel, Bishnu P. ^{[1
,2
,3
]}

Xu, Zhi-Qiang ^{[1
,2
,3
]}

Jergic, Slobodan ^{[1
,2
,3
]}

Oakley, Aaron J. ^{[1
,2
,3
]}

Sharma, Nischal ^{[1
,2
,3
]}

Brown, Simon H. J. ^{[1
,2
,3
,4
]}

Bouwer, James C. ^{[1
,2
,3
,4
]}

Lewis, Peter J. ^{[1
,2
,5
]}

Dixon, Nicholas E. ^{[1
,2
,3
,4
]}

van Oijen, Antoine M. ^{[1
,2
,3
,4
]}

Ghodke, Harshad ^{[1
,2
,3
]}

机构：

[1] Univ Wollongong, Mol Horizons, Wollongong, NSW 2522, Australia

[2] Univ Wollongong, Sch Chem & Mol Biosci, Wollongong, NSW 2522, Australia

[3] Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia

[4] Univ Wollongong, ARC Ind Transformat Training Ctr Cryoelectron Mic, Wollongong, NSW 2522, Australia

[5] Univ Newcastle, Sch Environm & Life Sci, Callaghan, NSW 2308, Australia

来源：

NUCLEIC ACIDS RESEARCH | 2022年 / 50卷 / 10期

基金：

澳大利亚研究理事会; 美国国家卫生研究院;

关键词：

NUCLEOTIDE EXCISION-REPAIR; RNA-POLYMERASE; COCKAYNE-SYNDROME; STRUCTURAL BASIS; DNA-DAMAGE; BACTERIAL; 2-AMINOPURINE; ELONGATION; COMPLEXES; INITIATION;

D O I：

10.1093/nar/gkac449

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Elongation by RNA polymerase is dynamically modulated by accessory factors. The transcription-repair coupling factor (TRCF) recognizes paused/stalled RNAPs and either rescues transcription or initiates transcription termination. Precisely how TRCFs choose to execute either outcome remains unclear. With Escherichia coli as a model, we used single-molecule assays to study dynamic modulation of elongation by Mfd, the bacterial TRCF. We found that nucleotide-bound Mfd converts the elongation complex (EC) into a catalytically poised state, presenting the EC with an opportunity to restart transcription. After long-lived residence in this catalytically poised state, ATP hydrolysis by Mfd remodels the EC through an irreversible process leading to loss of the RNA transcript. Further, biophysical studies revealed that the motor domain of Mfd binds and partially melts DNA containing a template strand overhang. The results explain pathway choice determining the fate of the EC and provide a molecular mechanism for transcription modulation by TRCF.

引用

页码：5688 / 5712

页数：25

共 65 条

[1] Structural Basis of Transcription: RNA Polymerase Backtracking and Its Reactivation [J].