Conserved Trigger Loop Histidine of RNA Polymerase II Functions as a Positional Catalyst Primarily through Steric Effects

Biochemistry ◽  
2021 ◽  
Author(s):  
Michael Z. Palo ◽  
Junqiao Zhu ◽  
Tatiana V. Mishanina ◽  
Robert Landick
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Steric Effects ◽  
Trigger Loop

scholarly journals Trigger loop dynamics mediate the balance between the transcriptional fidelity and speed of RNA polymerase II

2012 ◽  
Vol 109 (17) ◽  
pp. 6555-6560 ◽  
Author(s):  
M. H. Larson ◽  
J. Zhou ◽  
C. D. Kaplan ◽  
M. Palangat ◽  
R. D. Kornberg ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Trigger Loop ◽  
Loop Dynamics

scholarly journals Energetic and Structural Details of the Trigger-Loop Closing Transition in RNA Polymerase II

2013 ◽  
Vol 105 (3) ◽  
pp. 767-775 ◽  
Author(s):  
Beibei Wang ◽  
Alexander V. Predeus ◽  
Zachary F. Burton ◽  
Michael Feig
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Trigger Loop ◽  
Structural Details ◽  
Loop Closing

scholarly journals Mechanism of RNA polymerase II bypass of oxidative cyclopurine DNA lesions

2015 ◽  
Vol 112 (5) ◽  
pp. E410-E419 ◽  
Author(s):  
Celine Walmacq ◽  
Lanfeng Wang ◽  
Jenny Chong ◽  
Kathleen Scibelli ◽  
Lucyna Lubkowska ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Active Site ◽  
Dna Lesions ◽  
Abasic Site ◽  
Pol Ii ◽  
Dna Lesion ◽  
Trigger Loop ◽  
Pyrimidine Dimers ◽  
Bulky Dna Lesions

In human cells, the oxidative DNA lesion 8,5′-cyclo-2'-deoxyadenosine (CydA) induces prolonged stalling of RNA polymerase II (Pol II) followed by transcriptional bypass, generating both error-free and mutant transcripts with AMP misincorporated immediately downstream from the lesion. Here, we present biochemical and crystallographic evidence for the mechanism of CydA recognition. Pol II stalling results from impaired loading of the template base (5′) next to CydA into the active site, leading to preferential AMP misincorporation. Such predominant AMP insertion, which also occurs at an abasic site, is unaffected by the identity of the 5′-templating base, indicating that it derives from nontemplated synthesis according to an A rule known for DNA polymerases and recently identified for Pol II bypass of pyrimidine dimers. Subsequent to AMP misincorporation, Pol II encounters a major translocation block that is slowly overcome. Thus, the translocation block combined with the poor extension of the dA.rA mispair reduce transcriptional mutagenesis. Moreover, increasing the active-site flexibility by mutation in the trigger loop, which increases the ability of Pol II to accommodate the bulky lesion, and addition of transacting factor TFIIF facilitate CydA bypass. Thus, blocking lesion entry to the active site, translesion A rule synthesis, and translocation block are common features of transcription across different bulky DNA lesions.

scholarly journals High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop

PLoS Genetics ◽  
2016 ◽  
Vol 12 (11) ◽  
pp. e1006321 ◽  
Author(s):  
Chenxi Qiu ◽  
Olivia C. Erinne ◽  
Jui M. Dave ◽  
Ping Cui ◽  
Huiyan Jin ◽  
...  
Keyword(s):  
High Resolution ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Trigger Loop

scholarly journals The RNA Polymerase II Trigger Loop Functions in Substrate Selection and Is Directly Targeted by α-Amanitin

2008 ◽  
Vol 30 (5) ◽  
pp. 547-556 ◽  
Author(s):  
Craig D. Kaplan ◽  
Karl-Magnus Larsson ◽  
Roger D. Kornberg
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Substrate Selection ◽  
Trigger Loop

scholarly journals High-resolution phenotypic landscape of the RNA Polymerase II trigger loop

2016 ◽  
Author(s):  
Chenxi Qiu ◽  
Olivia C. Erinne ◽  
Jui Dave ◽  
Ping Cui ◽  
Huiyan Jin ◽  
...  
Keyword(s):  
High Resolution ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Active Site ◽  
Genetic Interactions ◽  
Substrate Selection ◽  
Phenotypic Data ◽  
Trigger Loop ◽  
Allele Specific ◽  
Individual Residue

The active site of multicellular RNA polymerases have a “trigger loop” (TL) that multitasks in substrate selection, catalysis, and translocation. To dissect the Saccharomyces cerevisiae RNA polymerase II TL at individual-residue resolution, we quantitatively phenotyped nearly all TL single variants en masse. Three major mutant classes, revealed by phenotypes linked to transcription defects or various stresses, have distinct distributions among TL residues. We find that mutations disrupting an intra-TL hydrophobic pocket, proposed to provide a mechanism for substrate-triggered TL folding through destabilization of a catalytically inactive TL state, confer phenotypes consistent with pocket disruption and increased catalysis. Furthermore, allele-specific genetic interactions among TL and TL-proximal domain residues support the contribution of the funnel and bridge helices (BH) to TL dynamics. Our structural genetics approach incorporates structural and phenotypic data for high-resolution dissection of transcription mechanisms and their evolution, and is readily applicable to other essential yeast proteins.

scholarly journals RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription

2010 ◽  
Vol 107 (36) ◽  
pp. 15745-15750 ◽  
Author(s):  
X. Huang ◽  
D. Wang ◽  
D. R. Weiss ◽  
D. A. Bushnell ◽  
R. D. Kornberg ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Trigger Loop
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