Transcription-coupled repair of 8-oxoguanine in human cells and its deficiency in some DNA repair diseases.

8-Oxoguanine (8-oxoG) is a major oxidized base found in DNA due to endogenous or exogenous pro-oxidant agents. In the absence of repair, this lesion has a high mutation potency giving rise mainly to G:C to A:T transversions. 8-oxoG can be removed by the classical base excision repair pathway but can also be eliminated by a transcription-coupled repair (TCR) process that needs the wild type activities of CSB, XPG, XPB, XPD, BRCA1, BRCA2 and MSH2 proteins. The lack of TCR of oxidative lesions may lead to dramatic hereditary diseases like Cockayne syndrome. Accumulation of unrepaired oxidized bases in brain cells may explain the progressive neurological deterioration found in some DNA repair-deficient patients.