Repair of 8-oxoguanine in DNA is deficient in Cockayne syndrome group B cells.
The incision of the 8-oxoguanine in DNA by normal and Cockayne Syndrome (CS) cell extracts has been investigated. The incision in extracts derived from CS cells was approximately 50% of the incision level compared with extracts prepared from normal cells. In contrast, the incision rate of uracil and thymine glycol was not defective in CS cells. The deficiency in 8-oxoguanine incision was also demonstrated in a CS family. Whereas the proband had markedly less incision compared with the normal siblings, the parents had intermediate levels. The low level of 8-oxoguanine-DNA glycosylase in CS extracts correlates with the reduced expression of the 8-oxoguanine-DNA glycosylase gene (hOGG1) in CS cells. Both the levels of expression of the hOGG1 gene and the incision of 8-oxoguanine in DNAincreased markedly after transfection of CS-B cells with the CSB gene. We suggest that the CSB mutation leads to deficient transcription of the hOGG1 gene and thus to deficient repair of 8-oxoguanine in DNA.
Dianov
G
G
Laboratory of Molecular Genetics, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Bischoff
C
C
Sunesen
M
M
Bohr
V A
VA
D001483:Base Sequence; D002460:Cell Line; D003057:Cockayne Syndrome / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D017931:DNA Primers; D004260:DNA Repair; D045643:DNA Repair Enzymes; D043382:DNA-Formamidopyrimidine Glycosylase; D015536:Down-Regulation; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D014162:Transfection