Poxvirus uracil‐DNA glycosylase—An unusual member of the family I uracil‐DNA glycosylases

Schormann, Norbert; Zhukovskaya, Natalia; Bedwell, Gregory; Nuth, Manunya; Gillilan, Richard; Prevelige, Peter E.; Ricciardi, Robert P.; Banerjee, Surajit; Chattopadhyay, Debasish

doi:10.1002/pro.3058

Poxvirus uracil‐DNA glycosylase—An unusual member of the family I uracil‐DNA glycosylases

Journal Article · Wed Nov 02 00:00:00 EDT 2016 · Protein Science

DOI:https://doi.org/10.1002/pro.3058· OSTI ID:1401237

Schormann, Norbert ^[1]; Zhukovskaya, Natalia ^[2]; Bedwell, Gregory ^[3]; ^[2]; Gillilan, Richard ^[4]; Prevelige, Peter E. ^[3]; Ricciardi, Robert P. ^[5]; Banerjee, Surajit ^[6]; Chattopadhyay, Debasish ^[1]

Department of Medicine University of Alabama at Birmingham Birmingham Alabama 35294
Department of Microbiology, School of Dental Medicine University of Pennsylvania Philadelphia Pennsylvania 19104
Department of Microbiology University of Alabama at Birmingham Birmingham Alabama 35294
MacCHESS (Macromolecular Diffraction Facility at CHESS) Cornell University Ithaca New York 14853
Department of Microbiology, School of Dental Medicine University of Pennsylvania Philadelphia Pennsylvania 19104, Abramson Cancer Center, School of Medicine University of Pennsylvania Philadelphia Pennsylvania 19104
Department of Chemistry and Chemical Biology Cornell University and NE‐CAT Argonne Illinois 60439

Abstract

Uracil‐DNA glycosylases are ubiquitous enzymes, which play a key role repairing damages in DNA and in maintaining genomic integrity by catalyzing the first step in the base excision repair pathway. Within the superfamily of uracil‐DNA glycosylases family I enzymes or UNGs are specific for recognizing and removing uracil from DNA. These enzymes feature conserved structural folds, active site residues and use common motifs for DNA binding, uracil recognition and catalysis. Within this family the enzymes of poxviruses are unique and most remarkable in terms of amino acid sequences, characteristic motifs and more importantly for their novel non‐enzymatic function in DNA replication. UNG of vaccinia virus, also known as D4, is the most extensively characterized UNG of the poxvirus family. D4 forms an unusual heterodimeric processivity factor by attaching to a poxvirus‐specific protein A20, which also binds to the DNA polymerase E9 and recruits other proteins necessary for replication. D4 is thus integrated in the DNA polymerase complex, and its DNA‐binding and DNA scanning abilities couple DNA processivity and DNA base excision repair at the replication fork. The adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three‐dimensional structure of D4. An overview of the current state of the knowledge on the structure‐function relationship of D4 is provided here.

View Accepted Manuscript (Publisher)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1401237

Alternate ID(s):: OSTI ID: 1335971

Journal Information:: Protein Science, Journal Name: Protein Science Journal Issue: 12 Vol. 25; ISSN 0961-8368

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: United Kingdom

Language:: English

References (43)

Uracil-DNA glycosylases-Structural and functional perspectives on an essential family of DNA repair enzymes: Uracil-DNA Glycosylases Schormann, N.; Ricciardi, R.; Chattopadhyay, D. Protein Science, Vol. 23, Issue 12 https://doi.org/10.1002/pro.2554	journal	October 2014
Mapping Interaction Sites of the A20R Protein Component of the Vaccinia Virus DNA Replication Complex Ishii, Koji; Moss, Bernard Virology, Vol. 303, Issue 2 https://doi.org/10.1006/viro.2002.1721	journal	November 2002
Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: Protein mimicry of DNA Mol, Clifford D.; Arvai, Andrew S.; Sanderson, Russell J. Cell, Vol. 82, Issue 5 https://doi.org/10.1016/0092-8674(95)90467-0	journal	September 1995
Vaccinia virus DNA polymerase. In vitro analysis of parameters affecting processivity. McDonald, W. F.; Traktman, P. Journal of Biological Chemistry, Vol. 269, Issue 49 https://doi.org/10.1016/S0021-9258(18)47408-X	journal	December 1994
Structure and function in the uracil-DNA glycosylase superfamily Pearl, Laurence H. Mutation Research/DNA Repair, Vol. 460, Issue 3-4 https://doi.org/10.1016/S0921-8777(00)00025-2	journal	August 2000
Lessons learned from structural results on uracil-DNA glycosylase Parikh, Sudip S.; Putnam, Christopher D.; Tainer, John A. Mutation Research/DNA Repair, Vol. 460, Issue 3-4 https://doi.org/10.1016/S0921-8777(00)00026-4	journal	August 2000
Clamp loaders and sliding clamps Jeruzalmi, David; O'Donnell, Mike; Kuriyan, John Current Opinion in Structural Biology, Vol. 12, Issue 2 https://doi.org/10.1016/S0959-440X(02)00313-5	journal	April 2002
Identification of polymerase and processivity inhibitors of vaccinia DNA synthesis using a stepwise screening approach Silverman, J.; Ciustea, M.; Shudofsky, A. Antiviral Research, Vol. 80, Issue 2 https://doi.org/10.1016/j.antiviral.2008.05.010	journal	November 2008
Inhibition of vaccinia virus replication by peptide aptamers Saccucci, Laurent; Crance, Jean-Marc; Colas, Pierre Antiviral Research, Vol. 82, Issue 3 https://doi.org/10.1016/j.antiviral.2009.02.191	journal	June 2009
A small molecule screen in yeast identifies inhibitors targeting protein–protein interactions within the vaccinia virus replication complex Flusin, Olivier; Saccucci, Laurent; Contesto-Richefeu, Céline Antiviral Research, Vol. 96, Issue 2 https://doi.org/10.1016/j.antiviral.2012.07.010	journal	November 2012
Mutations at Arginine 276 transform human uracil-DNA glycosylase into a single-stranded DNA-specific uracil-DNA glycosylase Chen, Cheng-Yao; Mosbaugh, Dale W.; Bennett, Samuel E. DNA Repair, Vol. 4, Issue 7 https://doi.org/10.1016/j.dnarep.2005.04.019	journal	July 2005
Crystal Structure of Family 5 Uracil-DNA Glycosylase Bound to DNA Kosaka, Hiromichi; Hoseki, Jun; Nakagawa, Noriko Journal of Molecular Biology, Vol. 373, Issue 4 https://doi.org/10.1016/j.jmb.2007.08.022	journal	November 2007
Uracil-DNA glycosylase: Structural, thermodynamic and kinetic aspects of lesion search and recognition Zharkov, Dmitry O.; Mechetin, Grigory V.; Nevinsky, Georgy A. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 685, Issue 1-2 https://doi.org/10.1016/j.mrfmmm.2009.10.017	journal	March 2010
Electrostatic Properties of Complexes along a DNA Glycosylase Damage Search Pathway Cravens, Shannen L.; Hobson, Matthew; Stivers, James T. Biochemistry, Vol. 53, Issue 48 https://doi.org/10.1021/bi501011m	journal	November 2014
Substrate Specificity of Homogeneous Monkeypox Virus Uracil-DNA Glycosylase ^† Duraffour, Sophie; Ishchenko, Alexander A.; Saparbaev, Murat Biochemistry, Vol. 46, Issue 42 https://doi.org/10.1021/bi700726a	journal	October 2007
Identification of Inhibitors that Block Vaccinia Virus Infection by Targeting the DNA Synthesis Processivity Factor D4 Nuth, Manunya; Huang, Lijuan; Saw, Yih Ling Journal of Medicinal Chemistry, Vol. 54, Issue 9 https://doi.org/10.1021/jm101554k	journal	May 2011
Design of Potent Poxvirus Inhibitors of the Heterodimeric Processivity Factor Required for Viral Replication Nuth, Manunya; Guan, Hancheng; Zhukovskaya, Natalia Journal of Medicinal Chemistry, Vol. 56, Issue 8 https://doi.org/10.1021/jm301735k	journal	April 2013
Identification of Non-Nucleoside DNA Synthesis Inhibitors of Vaccinia Virus by High-Throughput Screening Ciustea, Mihai; Silverman, Janice Elaine Y.; Druck Shudofsky, Abigail M. Journal of Medicinal Chemistry, Vol. 51, Issue 20 https://doi.org/10.1021/jm800366g	journal	October 2008
A nucleotide-flipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA Slupphaug, Geir; Mol, Clifford D.; Kavli, Bodil Nature, Vol. 384, Issue 6604 https://doi.org/10.1038/384087a0	journal	November 1996
Enzymatic capture of an extrahelical thymine in the search for uracil in DNA Parker, Jared B.; Bianchet, Mario A.; Krosky, Daniel J. Nature, Vol. 449, Issue 7161 https://doi.org/10.1038/nature06131	journal	August 2007
DNA Structure Changes Coupled to Protein Binding Dlakic, Mensur; Kerppola, Tom K. Encyclopedia of Life Sciences https://doi.org/10.1038/npg.els.0003009	book	April 2001
Genome-wide analysis of vaccinia virus protein-protein interactions McCraith, S.; Holtzman, T.; Moss, B. Proceedings of the National Academy of Sciences, Vol. 97, Issue 9 https://doi.org/10.1073/pnas.080078197	journal	April 2000
Uracil DNA glycosylase uses DNA hopping and short-range sliding to trap extrahelical uracils Porecha, R. H.; Stivers, J. T. Proceedings of the National Academy of Sciences, Vol. 105, Issue 31 https://doi.org/10.1073/pnas.0801612105	journal	July 2008
Evaluation of the Role of the Vaccinia Virus Uracil DNA Glycosylase and A20 Proteins as Intrinsic Components of the DNA Polymerase Holoenzyme Boyle, Kathleen A.; Stanitsa, Eleni S.; Greseth, Matthew D. Journal of Biological Chemistry, Vol. 286, Issue 28 https://doi.org/10.1074/jbc.M111.222216	journal	May 2011
New Family of Deamination Repair Enzymes in Uracil-DNA Glycosylase Superfamily Lee, Hyun-Wook; Dominy, Brian N.; Cao, Weiguo Journal of Biological Chemistry, Vol. 286, Issue 36 https://doi.org/10.1074/jbc.M111.249524	journal	June 2011
Crystal Structure of the Vaccinia Virus Uracil-DNA Glycosylase in Complex with DNA Burmeister, Wim P.; Tarbouriech, Nicolas; Fender, Pascal Journal of Biological Chemistry, Vol. 290, Issue 29 https://doi.org/10.1074/jbc.M115.648352	journal	June 2015
Vaccinia Virus Uracil DNA Glycosylase Interacts with the A20 Protein to Form a Heterodimeric Processivity Factor for the Viral DNA Polymerase Stanitsa, Eleni S.; Arps, Lisa; Traktman, Paula Journal of Biological Chemistry, Vol. 281, Issue 6 https://doi.org/10.1074/jbc.M511239200	journal	December 2005
Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA Parikh, S. S. The EMBO Journal, Vol. 17, Issue 17 https://doi.org/10.1093/emboj/17.17.5214	journal	September 1998
A novel uracil-DNA glycosylase family related to the helix-hairpin-helix DNA glycosylase superfamily Chung, J. H. Nucleic Acids Research, Vol. 31, Issue 8 https://doi.org/10.1093/nar/gkg319	journal	April 2003
Characterisation of the substrate specificity of homogeneous vaccinia virus uracil-DNA glycosylase Scaramozzino, N. Nucleic Acids Research, Vol. 31, Issue 16 https://doi.org/10.1093/nar/gkg672	journal	August 2003
Crystallization and preliminary X-ray diffraction analysis of three recombinant mutants of Vaccinia virus uracil DNA glycosylase Sartmatova, Darika; Nash, Taishayla; Schormann, Norbert Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 69, Issue 3 https://doi.org/10.1107/S1744309113002716	journal	February 2013
Structure of the uracil complex of Vaccinia virus uracil DNA glycosylase Schormann, N.; Banerjee, S.; Ricciardi, R. Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 69, Issue 12 https://doi.org/10.1107/S1744309113030613	journal	November 2013
Structural analysis of point mutations at the Vaccinia virus A20/D4 interface Contesto-Richefeu, Céline; Tarbouriech, Nicolas; Brazzolotto, Xavier Acta Crystallographica Section F Structural Biology Communications, Vol. 72, Issue 9 https://doi.org/10.1107/S2053230X16011778	journal	August 2016
Identification of Protein-Protein Interaction Inhibitors Targeting Vaccinia Virus Processivity Factor for Development of Antiviral Agents Schormann, Norbert; Sommers, Charnell Inglis; Prichard, Mark N. Antimicrobial Agents and Chemotherapy, Vol. 55, Issue 11 https://doi.org/10.1128/AAC.00278-11	journal	August 2011
Domain Organization of Vaccinia Virus Helicase-Primase D5 Hutin, Stephanie; Ling, Wai Li; Round, Adam Journal of Virology, Vol. 90, Issue 9 https://doi.org/10.1128/JVI.00044-16	journal	February 2016
Vaccinia Virus D4 Mutants Defective in Processive DNA Synthesis Retain Binding to A20 and DNA Druck Shudofsky, A. M.; Silverman, J. E. Y.; Chattopadhyay, D. Journal of Virology, Vol. 84, Issue 23 https://doi.org/10.1128/JVI.01435-10	journal	September 2010
Low-Resolution Structure of Vaccinia Virus DNA Replication Machinery Sèle, Céleste; Gabel, Frank; Gutsche, Irina Journal of Virology, Vol. 87, Issue 3 https://doi.org/10.1128/JVI.01533-12	journal	November 2012
Role of Vaccinia Virus A20R Protein in DNA Replication: Construction and Characterization of Temperature-Sensitive Mutants Ishii, K.; Moss, B. Journal of Virology, Vol. 75, Issue 4 https://doi.org/10.1128/JVI.75.4.1656-1663.2001	journal	February 2001
Vaccinia Virus Uracil DNA Glycosylase Has an Essential Role in DNA Synthesis That Is Independent of Its Glycosylase Activity: Catalytic Site Mutations Reduce Virulence but Not Virus Replication in Cultured Cells De Silva, F. S.; Moss, B. Journal of Virology, Vol. 77, Issue 1 https://doi.org/10.1128/JVI.77.1.159-166.2003	journal	January 2003
Mutations in active-site residues of the uracil-DNA glycosylase encoded by vaccinia virus are incompatible with virus viability Ellison, K. S.; Peng, W.; McFadden, G. Journal of Virology, Vol. 70, Issue 11 https://doi.org/10.1128/jvi.70.11.7965-7973.1996	journal	November 1996
Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly Schormann, Norbert; Grigorian, Alexei; Samal, Alexandra BMC Structural Biology, Vol. 7, Issue 1 https://doi.org/10.1186/1472-6807-7-45	journal	January 2007
Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA Glycosylase Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert BMC Structural Biology, Vol. 15, Issue 1 https://doi.org/10.1186/s12900-015-0037-1	journal	June 2015
Crystal Structure of the Vaccinia Virus DNA Polymerase Holoenzyme Subunit D4 in Complex with the A20 N-Terminal Domain Contesto-Richefeu, Céline; Tarbouriech, Nicolas; Brazzolotto, Xavier PLoS Pathogens, Vol. 10, Issue 3 https://doi.org/10.1371/journal.ppat.1003978	journal	March 2014

Similar Records

Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase

Journal Article · Wed Nov 02 00:00:00 EDT 2016 · Protein Science · OSTI ID:1335971

Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

Journal Article · Tue Jun 02 00:00:00 EDT 2015 · BMC Structural Biology (Online) · OSTI ID:1224087

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly

Journal Article · Mon Jul 02 00:00:00 EDT 2007 · BMC Structural Biology (Online) · OSTI ID:1626553

Poxvirus uracil‐DNA glycosylase—An unusual member of the family I uracil‐DNA glycosylases

Citation Formats

References (43)

Similar Records

Related Subjects