Nucleotide excision repair (NER) machinery recruitment by the transcription-repair coupling factor involves unmasking of a conserved intramolecular interface.

Proceedings of the National Academy of Sciences of the United States of America
Alexandra M DeaconescuNikolaus Grigorieff

Abstract

Transcription-coupled DNA repair targets DNA lesions that block progression of elongating RNA polymerases. In bacteria, the transcription-repair coupling factor (TRCF; also known as Mfd) SF2 ATPase recognizes RNA polymerase stalled at a site of DNA damage, removes the enzyme from the DNA, and recruits the Uvr(A)BC nucleotide excision repair machinery via UvrA binding. Previous studies of TRCF revealed a molecular architecture incompatible with UvrA binding, leaving its recruitment mechanism unclear. Here, we examine the UvrA recognition determinants of TRCF using X-ray crystallography of a core TRCF-UvrA complex and probe the conformational flexibility of TRCF in the absence and presence of nucleotides using small-angle X-ray scattering. We demonstrate that the C-terminal domain of TRCF is inhibitory for UvrA binding, but not RNA polymerase release, and show that nucleotide binding induces concerted multidomain motions. Our studies suggest that autoinhibition of UvrA binding in TRCF may be relieved only upon engaging the DNA damage.

References

Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·C P SelbyA Sancar
Sep 1, 1990·Mutation Research·C P Selby, A Sancar
Mar 3, 1995·The Journal of Biological Chemistry·C P Selby, A Sancar
Dec 1, 1993·Journal of Bacteriology·C P Selby, A Sancar
Apr 2, 1993·Science·C P Selby, A Sancar
Jun 6, 2003·Journal of Molecular Biology·Robert S WashburnMax E Gottesman
Apr 6, 2004·Current Opinion in Microbiology·Jeffrey Roberts, Joo-Seop Park
Jun 12, 2004·The EMBO Journal·James J TruglioCaroline Kisker
Nov 29, 2005·Journal of Molecular Biology·Nora AssenmacherKarl-Peter Hopfner
Feb 14, 2006·Cell·Alexandra M DeaconescuSeth A Darst
Mar 3, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Alexandra M Deaconescu, Seth A Darst
Mar 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Joo-Seop Park, Jeffrey W Roberts
Jan 24, 2007·Current Opinion in Structural Biology·Alexandra M DeaconescuSeth A Darst
Nov 22, 2008·Nature Reviews. Molecular Cell Biology·Philip C Hanawalt, Graciela Spivak
Mar 17, 2009·The Journal of Biological Chemistry·Danaya PakotipraphaDavid Jeruzalmi
Sep 22, 2009·Diagnostic Microbiology and Infectious Disease·Gin Hyug LeeJin-Ho Kim
Jan 30, 2010·Science·Richard T Pomerantz, Mike O'Donnell
Aug 13, 2010·Nucleic Acids Research·Lars F WestbladeSeth A Darst
Dec 15, 2010·Molecular Cell·Laura ManelyteNigel J Savery
Dec 28, 2010·Journal of Molecular Biology·Devendra B Srivastava, Seth A Darst
Oct 15, 2011·Current Opinion in Structural Biology·Glenn Hauk, Gregory D Bowman

❮ Previous
Next ❯

Citations

Aug 21, 2012·Nucleic Acids Research·Abigail J SmithNigel J Savery
Mar 5, 2013·Cold Spring Harbor Perspectives in Biology·Caroline KiskerBennett Van Houten
Feb 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Nia M HainesNigel J Savery
Oct 23, 2012·Trends in Biochemical Sciences·Alexandra M DeaconescuNikolaus Grigorieff
Dec 19, 2015·BMC Microbiology·Stephanie E WillingNeil F Fairweather
Jul 2, 2015·Annual Review of Microbiology·Georgiy A Belogurov, Irina Artsimovitch
Jun 13, 2013·Transcription·Jordan MonnetNicolas Joly
Jan 18, 2015·Current Opinion in Microbiology·Venu Kamarthapu, Evgeny Nudler
Nov 20, 2016·Photochemistry and Photobiology·Alexandra M Deaconescu, Margaret M Suhanovsky
Nov 20, 2016·Photochemistry and Photobiology·Christopher P Selby
Jun 29, 2013·Cellular and Molecular Life Sciences : CMLS·Alexandra M Deaconescu
Mar 17, 2017·Journal of Food Science and Technology·Taher Khakpour MoghaddamGuocheng Du
Mar 22, 2020·Nature Communications·Harshad GhodkeAntoine M van Oijen
Jul 29, 2020·Nature Communications·Christiane BruggerAlexandra M Deaconescu
Oct 18, 2020·Nucleic Acids Research·Jing ShiYu Feng
Oct 30, 2020·Biomolecules·Craig J Marshall, Thomas J Santangelo
Feb 16, 2021·Microbiological Research·Shuang HanJianping Xie
Jun 9, 2019·Journal of Molecular Biology·T R Strick, J R Portman
Jun 8, 2021·Frontiers in Molecular Biosciences·Laura A Lindsey-Boltz, Aziz Sancar

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.