Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product.
Cockayne syndrome (CS) is an autosomal recessive human disease characterized by UV-sensitivity as well as neurological and developmental abnormalities. Two complementation groups have been established, designated CS-A and CS-B. Traditionally, CSA and CSB have been ascribed a function in the transcription-coupled repair (TCR) pathway of nucleotide excision repair (NER) that efficiently removes bulky lesions from the transcribed strand of RNA polymerase II transcribed genes. To assess the role of the CSB protein in the repair of the highly mutagenic base lesion 7,8-dihydro-8-oxoguanine (8-oxoG), we have investigated the removal of this lesion using an in vitro incision approach with cell extracts as well as an in vivo approach with a modified protocol of the gene-specific repair assay, which allows the measurement of base lesion repair in intragenomic sequences. Our results demonstrate that the integrity of the CSB protein is pivotal for processes leading to incision at the site of 8-oxoG and that the global genome repair (GGR) of this lesion requires a functional CSB gene product in vivo.
Sunesen
Morten
M
Department of Molecular and Structural Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.
Stevnsner
Tinna
T
Brosh
Robert M
RM
Dianov
Grigory L
GL
Bohr
Vilhelm A
VA
D000251:Adenosine Triphosphatases / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D016678:Genome; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D008027:Light; D008969:Molecular Sequence Data; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000737:chemistry; D017319:Photosensitizing Agents / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011759:Pyrrolidines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D016415:Sequence Alignment; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D017319:Photosensitizing Agents; D011759:Pyrrolidines; D011807:Quinolizines; C076809:Ro 19-8022; D006151:Guanosine; C046215:8-hydroxyguanosine; D013762:Tetrahydrofolate Dehydrogenase; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D000251:Adenosine Triphosphatases; D004265:DNA Helicases