Lessons learned from structural results on uracil-DNA glycosylase

Sudip S. Parikh; Christopher D. Putnam; John A. Tainer

doi:10.1016/S0921-8777(00)00026-4

Lessons learned from structural results on uracil-DNA glycosylase

Sudip S. Parikh, Christopher D. Putnam, John A. Tainer

Research output: Contribution to journal › Article › peer-review

119 Scopus citations

Abstract

Uracil-DNA glycosylase (UDG) functions as a sentry guarding against uracil in DNA. UDG initiates DNA base excision repair (BER) by hydrolyzing the uracil base from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and complete functional mechanism is emerging that combines structural and biochemical results. This functional mechanism addresses the detection of uracil bases within a vast excess of normal DNA, the features of the enzyme that drive catalysis, and coordination of UDG with later steps of BER while preventing the release of toxic intermediates. Many of the solutions that UDG has evolved to overcome the challenges of policing the genome are shared by other DNA glycosylases and DNA repair enzymes, and thus appear to be general. (C) 2000 Elsevier Science B.V.

Original language	English (US)
Pages (from-to)	183-199
Number of pages	17
Journal	Mutation Research - DNA Repair
Volume	460
Issue number	3-4
DOIs	https://doi.org/10.1016/S0921-8777(00)00026-4
State	Published - Aug 30 2000
Externally published	Yes

Keywords

DNA base excision repair
Enzyme mechanism
Protein structure
Uracil-DNA glycosylase

ASJC Scopus subject areas

Molecular Biology
Toxicology
Genetics

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10.1016/S0921-8777(00)00026-4

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title = "Lessons learned from structural results on uracil-DNA glycosylase",

abstract = "Uracil-DNA glycosylase (UDG) functions as a sentry guarding against uracil in DNA. UDG initiates DNA base excision repair (BER) by hydrolyzing the uracil base from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and complete functional mechanism is emerging that combines structural and biochemical results. This functional mechanism addresses the detection of uracil bases within a vast excess of normal DNA, the features of the enzyme that drive catalysis, and coordination of UDG with later steps of BER while preventing the release of toxic intermediates. Many of the solutions that UDG has evolved to overcome the challenges of policing the genome are shared by other DNA glycosylases and DNA repair enzymes, and thus appear to be general. (C) 2000 Elsevier Science B.V.",

keywords = "DNA base excision repair, Enzyme mechanism, Protein structure, Uracil-DNA glycosylase",

author = "Parikh, {Sudip S.} and Putnam, {Christopher D.} and Tainer, {John A.}",

note = "Funding Information: This work could not have been possible without expert collaborations with the laboratories of H.E. Krokan, D.W. Mosbaugh, G.M. Blackburn, and G. Slupphaug. We thank C.D. Mol, D.J. Hosfield, and K.E. Morgan for helpful discussions, as well as the staff and facilities at the Stanford Synchrotron Radiation Laboratory, the BioCARS at the Advanced Photon Source, the National Synchrotron Light Source at Brookhaven National Laboratory, and the Cornell High Energy Synchrotron Source. Work on DNA repair in the authors' laboratory is supported by the National Institutes of Health grant GM46312 (JAT), The Skaggs Institute for Chemical Biology (JAT,SSP), and graduate research fellowships from the Howard Hughes Medical Institute (CDP) and the National Science Foundation (SSP).",

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N2 - Uracil-DNA glycosylase (UDG) functions as a sentry guarding against uracil in DNA. UDG initiates DNA base excision repair (BER) by hydrolyzing the uracil base from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and complete functional mechanism is emerging that combines structural and biochemical results. This functional mechanism addresses the detection of uracil bases within a vast excess of normal DNA, the features of the enzyme that drive catalysis, and coordination of UDG with later steps of BER while preventing the release of toxic intermediates. Many of the solutions that UDG has evolved to overcome the challenges of policing the genome are shared by other DNA glycosylases and DNA repair enzymes, and thus appear to be general. (C) 2000 Elsevier Science B.V.

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Lessons learned from structural results on uracil-DNA glycosylase

Abstract

Keywords

ASJC Scopus subject areas

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