Chemistry of Life

Molecular genetics, biochemistry

oxidative stress and DNA damage

Oxidative Stress/DNA Damage and DNA Repair: "Oxidative stress is produced in cells by oxygen-derived species resulting from cellular metabolism and from interaction with cells of exogenous sources such as carcinogenic compounds, redox-cycling drugs and ionizing radiations. DNA damage caused by oxygen-derived species including free radicals is the most frequent type encountered by aerobic cells. DNA damage caused by oxygen-derived species including free radicals is the most frequent type encountered by aerobic cells. When this type of damage occurs to DNA, it is called oxidative DNA damage and it can produce a multiplicity of modifications in DNA including base and sugar lesions, strand breaks, DNA-protein cross-links and base-free sites. "

MOLECULAR BIOLOGY: ON DNA-REPAIR ENZYMESThe agents that cause oxidative damage to DNA include oxygen radicals and ionizing radiation. Oxidation of a guanosine base to form oxoG produces a subtle structural transformation that results in deleterious mutations because DNA polymerases misread oxoG as a thymine (T) during genome replication prior to cell division. The human oxoG repair enzyme (hOGG1) catalyses the excision of oxoG in the first step of base excision repair. Structural studies of the glycosylase enzymes involved in the repair process reveal common features of damaged-base recognition. These include enzyme-initiated DNA distortion that flips the damaged base out from the DNA double helix for recognition within a base-specific cavity of the enzyme.

(OGG1)MOLECULAR BIOLOGY: ON DNA-REPAIR ENZYMES: "hOGG1 makes extensive contacts with the orphaned cytosine base, which ensures that oxoG is removed only when in the appropriate base-pairing context. Although extensive biophysical and structural studies intimate that there are general features of damaged bases that signal their presence to repair enzymes, the steps involved in finding damaged bases in a sea of normal ones are still unclear. Most mechanisms invoke the enzyme sliding or hopping along the DNA duplex until a damaged site is detected. A particularly intriguing question is whether normal bases are also extruded from the helix during the search process."

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. . . transcription begun 10/06/06