Substantial evidence demonstrates that DNA repair processes are not distributed homogeneously throughout the genome but that lesions are removed more efficiently and at higher rates from active than from inactive genes. Transcription-coupled repair (TCR) appears to be a sophisticated subpathway of nucleotide excision repair (NER) that targets the repair machinery to lesions present in the actively transcribed strand; TCR could explain the preferential repair of the transcribed over the nontranscribed strand in active genes and involves ERCC2 and ERCC3 helicases in human cells, integral components of TFIIH, as well as ERCCG. XPC protein is responsible for the repair of inactive regions. In S. cerevisiae RAD16 helicase as well as RAD9 and RAD24 proteins are involved in repairing nontranscribing regions whereas RAD3 and SSL2 helicases, homologs of the human ERCC2 and ERCC3, function for the repair of active regions. Unraveling the mechanisms that govern the heterogeneous repair rates among active and inactive parts of the genome is important in understanding mechanisms of carcinogenesis.

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