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Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner. The importance of CSB degradation for post-transcription-coupled repair (TCR) recovery of transcription and for the Cockayne syndrome is demonstrated, which unravel for the first time the functional relationship between CSA and CSB.

Nucleotide excision repair (NER) is a repair mechanism that removes DNA lesions induced by UV radiation, environmental mutagens and carcinogens. There exists sufficient evidence against acetaldehyde suggesting it to cause a variety of DNA lesions and be carcinogenic to humans. Previously, we found that acetaldehyde induces reversible intra-strand GG crosslinks in DNA similar to those induced by cis -diammineplatinum(II) that is subsequently repaired by NER. In this study, we analysed the repairability by NER mechanism and the mutagenesis of acetaldehyde. In an in vitro reaction setup with NER-proficient and NER-deficient xeroderma pigmentosum group A (XPA) cell extracts, NER reactions were observed in the presence of XPA recombinant proteins in acetaldehyde-treated plasmids. Using an in vivo assay with living XPA cells and XPA-correcting XPA cells, the repair reactions were also observed. Additionally, it was observed that DNA polymerase eta inserted dATP opposite guanine in acetaldehyde-treated oligonucleotides, suggesting that acetaldehyde-induced GG-to-TT transversions. These findings show that acetaldehyde induces NER repairable mutagenic DNA lesions. [ABSTRACT FROM AUTHOR]

Research has been conducted on nucleoside excision repair. The authors demonstrate that UV response of the DDB2 and CSA complexes affect nucleoside excision repair mechanism.

Exposure of cellular DNA to reactive oxygen species generates several classes of base lesions, many of which are removed by the base excision-repair pathway. However, the lesions include purine cyclodeoxynucleoside formation by intramolecular crosslinking between the C-8 position of adenine or guanine and the 5' position of 2-deoxyribose. This distorting form of DNA damage, in which the purine is attached by two covalent bonds to the sugar-phosphate backbone, occurs as distinct diastereoisomers. It was observed here that both diastereoisomers block primer extension by mammalian and microbial replicative DNA polymerases, using DNA with a site-specific purine cyclodeoxynucleoside residue as template, and consequently appear to be cytotoxic lesions. Plasmid DNA containing either the 5'R or 5'S form of 5',8-cyclo-2-deoxyadenosine was a substrate for the human nucleotide excision-repair enzyme complex. The R diastereoisomer was more efficiently repaired than the S isomer. No correction of the lesion by direct damage reversal or base excision repair was detected. Dual incision around the lesion depended on the core nucleotide excision-repair protein XPA. In contrast to several other types of oxidative DNA damage, purine cyclodeoxynucleosides are chemically stable and would be expected to accumulate at a slow rate over many years in the DNA of nonregenerating cells from xeroderma pigmentosum patients. High levels of this form of DNA damage might explain the progressive neurodegeneration seen in XPA individuals.