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Mapping Oxidative DNA Damage and Mechanisms of Repair
Author(s) -
AKMAN STEVEN A.,
O'CONNOR TIMOTHY R.,
RODRIGUEZ HENRY
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06178.x
Subject(s) - dna damage , oxidative stress , base excision repair , dna , dna repair , in vivo , chemistry , reactive oxygen species , ligation , microbiology and biotechnology , base pair , in vitro , polymerase chain reaction , gene , biology , genetics , biochemistry
A bstract : We developed a method to map oxidative‐induced DNA damage at the nucleotide level using ligation‐mediated polymerase chain reaction (LMPCR) technology. In vivo and in vitro DNA base modification patterns inflicted by reactive oxygen species (ROS) in the human P53 and PGK1 gene were nearly identical in vitro and in vivo . In human male fibroblasts, these patterns are independent of the transition metal used (Cu (II), Fe(II), or Cr(VI)). Therefore, local probability of H 2 O 2 ‐mediated DNA base damage is determined primarily by DNA sequence. Moreover, in cells undergoing severe oxidative stress, extranuclear sites contribute metals that enhance nuclear DNA damage. The role of the base excision repair pathway in human cells responsible for the repair of the majority of ROS base damage is also discussed.