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

Abstract

We report that 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. In conclusion, the adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three-dimensionalmore » structure of D4. We provide an overview of the current state of the knowledge on the structure-function relationship of D4.« less

Authors:
 [1];  [2];  [3]; ORCiD logo [2];  [4];  [3];  [5];  [6];  [1]
  1. Department of Medicine, University of Alabama at Birmingham, Birmingham Alabama 35294
  2. Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104
  3. Department of Microbiology, University of Alabama at Birmingham, Birmingham Alabama 35294
  4. MacCHESS (Macromolecular Diffraction Facility at CHESS) Cornell University, Ithaca New York 14853
  5. 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
  6. Department of Chemistry and Chemical Biology, Cornell University, and NE-CAT Argonne Illinois 60439
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
DOE - BASIC ENERGY SCIENCESNSFNIH
OSTI Identifier:
1335971
Resource Type:
Journal Article
Journal Name:
Protein Science
Additional Journal Information:
Journal Volume: 25; Journal Issue: 12; Journal ID: ISSN 0961-8368
Publisher:
The Protein Society
Country of Publication:
United States
Language:
ENGLISH
Subject:
uracil-DNA glycosylase; poxvirus; processivity factor; DNA polymerase holoenzyme; DNA repair; replication; antiviral agents

Citation Formats

Schormann, Norbert, Zhukovskaya, Natalia, Bedwell, Gregory, Nuth, Manunya, Gillilan, Richard, Prevelige, Peter E., Ricciardi, Robert P., Banerjee, Surajit, and Chattopadhyay, Debasish. Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase. United States: N. p., 2016. Web. doi:10.1002/pro.3058.
Schormann, Norbert, Zhukovskaya, Natalia, Bedwell, Gregory, Nuth, Manunya, Gillilan, Richard, Prevelige, Peter E., Ricciardi, Robert P., Banerjee, Surajit, & Chattopadhyay, Debasish. Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase. United States. doi:10.1002/pro.3058.
Schormann, Norbert, Zhukovskaya, Natalia, Bedwell, Gregory, Nuth, Manunya, Gillilan, Richard, Prevelige, Peter E., Ricciardi, Robert P., Banerjee, Surajit, and Chattopadhyay, Debasish. Wed . "Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase". United States. doi:10.1002/pro.3058.
@article{osti_1335971,
title = {Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases: Poxvirus Uracil-DNA Glycosylase},
author = {Schormann, Norbert and Zhukovskaya, Natalia and Bedwell, Gregory and Nuth, Manunya and Gillilan, Richard and Prevelige, Peter E. and Ricciardi, Robert P. and Banerjee, Surajit and Chattopadhyay, Debasish},
abstractNote = {We report that 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. In conclusion, the adaptations necessary for taking on the new function are reflected in the amino acid sequence and the three-dimensional structure of D4. We provide an overview of the current state of the knowledge on the structure-function relationship of D4.},
doi = {10.1002/pro.3058},
journal = {Protein Science},
issn = {0961-8368},
number = 12,
volume = 25,
place = {United States},
year = {2016},
month = {11}
}