Enzymatic Processing of Uracil Glycol, a Major Oxidative Product of DNA Cytosine

A major stable oxidation product of DNA cytosine is uracil glycol (Ug). Because of the potential of Ug to be a strong premutagenic lesion, it is important to assess whether it is a blocking lesion to DNA polymerase as is its structural counterpart, thymine glycol (Tg), and to evaluate its pairing pr...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1998-04, Vol.273 (16), p.10026-10035
Main Authors: Purmal, A A, Lampman, G W, Bond, J P, Hatahet, Z, Wallace, S S
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Base Composition
Base Sequence
Cytosine
Deoxyadenine Nucleotides - metabolism
DNA - chemistry
DNA - metabolism
DNA Damage
DNA Polymerase I - metabolism
DNA Primers
DNA Repair
Escherichia coli - enzymology
Kinetics
Models, Molecular
Molecular Sequence Data
Nucleic Acid Conformation
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - metabolism
Oxidation-Reduction
Templates, Genetic
Thymine - analogs & derivatives
Thymine - metabolism
Uracil - analogs & derivatives
Uracil - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A major stable oxidation product of DNA cytosine is uracil glycol (Ug). Because of the potential of Ug to be a strong premutagenic lesion, it is important to assess whether it is a blocking lesion to DNA polymerase as is its structural counterpart, thymine glycol (Tg), and to evaluate its pairing properties. Here, a series of oligonucleotides containing Ug or Tg were prepared and used as templates for a model enzyme, Escherichia coli DNA polymerase I Klenow fragment (exo − ). During translesion DNA synthesis, Ug was bypassed more efficiently than Tg in all sequence contexts examined. Furthermore, only dAMP was incorporated opposite template Ug and Tg and the kinetic parameters of incorporation showed that dAMP was inserted opposite Ug more efficiently than opposite Tg. Ug opposite G and A was also recognized and removed in vitro by the E. coli DNA repair glycosylases, endonuclease III (endo III), endonuclease VIII (endo VIII), and formamidopyrimidine DNA glycosylase. The steady state kinetic parameters indicated that Ug was a better substrate for endo III and formamidopyrimidine DNA glycosylase than Tg; for endonuclease VIII, however, Tg was a better substrate.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.16.10026