Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage

DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and dise...

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Main Authors: Robert L. Eoff, Jeong-Yun Choi, F. Peter Guengerich
Format: Article
Language:English
Published: Wiley 2010-01-01
Series:Journal of Nucleic Acids
Online Access:http://dx.doi.org/10.4061/2010/830473
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author Robert L. Eoff
Jeong-Yun Choi
F. Peter Guengerich
author_facet Robert L. Eoff
Jeong-Yun Choi
F. Peter Guengerich
author_sort Robert L. Eoff
collection DOAJ
description DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members.
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spelling doaj-art-0fa95d2b0d51421e9f1fac39904e18792025-02-03T05:50:23ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/830473830473Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA DamageRobert L. Eoff0Jeong-Yun Choi1F. Peter Guengerich2Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USADepartment of Pharmacology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of KoreaDepartment of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN 37232-0146, USADNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members.http://dx.doi.org/10.4061/2010/830473
spellingShingle Robert L. Eoff
Jeong-Yun Choi
F. Peter Guengerich
Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
Journal of Nucleic Acids
title Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
title_full Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
title_fullStr Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
title_full_unstemmed Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
title_short Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage
title_sort mechanistic studies with dna polymerases reveal complex outcomes following bypass of dna damage
url http://dx.doi.org/10.4061/2010/830473
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