Transcription-Coupled DNA Repair

Abstract

Certain DNA lesions are removed preferentially from the transcribed strands of active genes in bacteria, yeast and mammalian cells. Initially it was thought that only lesions removed by nucleotide excision repair (NER) were subject to this pathway of transcription-coupled repair (TCR), but recent investigations have shown that some lesions caused by reactive oxygen species, that are recognized by glycosylases and are subject to base excision repair (BER), can be preferentially repaired in the transcribed strands of active genes in mammalian cells. We will discuss the pathways and the proteins involved in the repair of different lesions or groups of lesions, produced by environmental agents or endogenous metabolic activities. The victims of the human hereditary diseases, xeroderma pig-mentosum (XP) and Cockayne syndrome (CS) are highly sensitive to DNA lesions induced by sunlight but only the former exhibit predisposition to cancer. While XP patients are generally deficient in NER, those with CS are specifically defective in TCR and are characterized by dwarfism and severe developmental abnormalities. The role of TCR in human health will be discussed with specific consideration of the problems of cancer and early development.