Defective repair of oxidative damage in the mitochondrial DNA of a xeroderma pigmentosum group A cell line.
Recent evidence has linked mitochondrial DNA (mtDNA) damage to several disease processes,including cancer and aging. An important source of such damage is reactive oxygen species. These molecules can be generated endogenously via the electron transport system or may arise from a host of exogenous sources. It has been reported that extracts from cells of individuals with xeroderma pigmentosum group A (XP-A) do not repair some types of oxidative DNA damage. The current experiments were designed to determine whether there is a correlation between the inadequate repair of oxidatively damaged nuclear DNA in XP-A cells and the capacity of such cells to repair similar damage to their mtDNA. The ability of karyotypically normal human fibroblasts (WI-38) and XP-A fibroblasts to repair alloxan-generated oxidative damage to nuclear and mtDNA was assessed using a quantitative Southern blot method in conjunction with the repair enzymes endonuclease III and formamidopyrimidine DNA glycosylase. The data indicate that both nuclear and mtDNA repair of each damage type investigated is more efficient in the WI-38 cells. These findings suggest a similarity between the process(es) used to repair oxidative damage to nuclear and mtDNA in that both are inhibited by the defect in XP-A.
Driggers
W J
WJ
Department of Structural and Cellular Biology, University of South Alabama, Mobile 36688, USA.
Grishko
V I
VI
LeDoux
S P
SP
Wilson
G L
GL
D000496:Alloxan / Q000008:administration & dosage / Q000494:pharmacology*; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D017382:Reactive Oxygen Species / Q000633:toxicity*; D013997:Time Factors; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D000496:Alloxan; D004247:DNA