The cockayne syndrome group B gene product is involved in cellular repair of 8-hydroxyadenine in DNA.
Cockayne syndrome (CS) is a human disease characterized by sensitivity to sunlight, severe neurological abnormalities, and accelerated aging. CS has two complementation groups, CS-A and CS-B. The CSB gene encodes the CSB protein with 1493 amino acids. We previously reported that the CSB protein is involved in cellular repair of 8-hydroxyguanine, an abundant lesion in oxidatively damaged DNA and that the putative helicase motif V/VI of the CSB may play a role in this process. The present study investigated the role of the CSB protein in cellular repair of 8-hydroxyadenine (8-OH-Ade), another abundant lesion in oxidatively damaged DNA. Extracts of CS-B-null cells and mutant cells with site-directed mutation in the motif VI of the putative helicase domain incised 8-hydroxyadenine in vitro less efficiently than wild type cells. Furthermore, CS-B-null and motif VI mutant cells accumulated more 8-hydroxyadenine in their genomic DNA than wild type cells after exposure to gamma-radiation at doses of 2 or 5 Gy. These results suggest that the CSB protein contributes to cellular repair of 8-OH-Ade and that the motif VI of the putative helicase domain of CSB is required for this activity.
Tuo
Jingsheng
J
Laboratory of Molecular Gerontology, National Institute on Aging/NIH, Baltimore, MD 21224, USA.
Jaruga
Pawel
P
Rodriguez
Henry
H
Dizdaroglu
Miral
M
Bohr
Vilhelm A
VA
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004265:DNA Helicases / Q000502:physiology*; D004260:DNA Repair; D045643:DNA Repair Enzymes; D005720:Gamma Rays; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins
D000075223:Poly-ADP-Ribose Binding Proteins; C002992:8-hydroxyadenine; C024829:8-hydroxyguanine; D006147:Guanine; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes; D000225:Adenine