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DNA repair: models for damage and mismatch recognition

Rajski, Scott R. and Jackson, Brian A. and Barton, Jacqueline K. (2000) DNA repair: models for damage and mismatch recognition. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 447 (1). pp. 49-72. ISSN 0027-5107 . http://resolver.caltech.edu/CaltechAUTHORS:20160127-111126763

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Abstract

Maintaining the integrity of the genome is critical for the survival of any organism. To achieve this, many families of enzymatic repair systems which recognize and repair DNA damage have evolved. Perhaps most intriguing about the workings of these repair systems is the actual damage recognition process. What are the chemical characteristics which are common to sites of nucleic acid damage that DNA repair proteins may exploit in targeting sites? Importantly, thermodynamic and kinetic principles, as much as structural factors, make damage sites distinct from the native DNA bases, and indeed, in many cases, these are the features which are believed to be exploited by repair enzymes. Current proposals for damage recognition may not fulfill all of the demands required of enzymatic repair systems given the sheer size of many genomes, and the efficiency with which the genome is screened for damage. Here we discuss current models for how DNA damage recognition may occur and the chemical characteristics, shared by damaged DNA sites, of which repair proteins may take advantage. These include recognition based upon the thermodynamic and kinetic instabilities associated with aberrant sites. Additionally, we describe how small changes in base pair structure can alter also the unique electronic properties of the DNA base pair π-stack. Further, we describe photophysical, electrochemical, and biochemical experiments in which mismatches and other local perturbations in structure are detected using DNA-mediated charge transport. Finally, we speculate as to how this DNA electron transfer chemistry might be exploited by repair enzymes in order to scan the genome for sites of damage.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/S0027-5107(99)00195-5DOIArticle
http://www.sciencedirect.com/science/article/pii/S0027510799001955PublisherArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2000 Elsevier Science B.V. Received 24 August 1999; received in revised form 3 September 1999; accepted 6 September 1999. We are grateful to the NIH for their financial support of our research. In addition we thank the American Cancer Society (to S.R.R.)., the National Science Foundation (to B.A.J.)., and the Parsons Foundation (to B.A.J.) for fellowship support. We are also grateful to Dr. R.J. Melamede for providing preprints detailing work in his laboratories at University of Vermont.
Funders:
Funding AgencyGrant Number
American Cancer SocietyUNSPECIFIED
NSFUNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
Subject Keywords:Energetic recognition; DNA repair; Base flipping; Pinch–push–pull; DNA-mediated electron transfer; Oxidative damage; Long-range charge transfer
Record Number:CaltechAUTHORS:20160127-111126763
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160127-111126763
Official Citation:Scott R Rajski, Brian A Jackson, Jacqueline K Barton, DNA repair: models for damage and mismatch recognition, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Volume 447, Issue 1, 17 January 2000, Pages 49-72, ISSN 0027-5107, http://dx.doi.org/10.1016/S0027-5107(99)00195-5. (http://www.sciencedirect.com/science/article/pii/S0027510799001955)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64008
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:27 Jan 2016 20:03
Last Modified:27 Jan 2016 20:03

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