Molecular genetic analysis of cellular response to transcription-blocking DNA damage and its defective disorders

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Nucleotide excision repair (NER) is a versatile DNA repair system that removes a wide range of DNA lesions including UV-damage and oxidative DNA damage. The importance of NER is indicated by the study of xeroderma pigmentosum patients who show a high incidence of skin cancer and neurological abnormalities, and are deficient in NER. Transcription-blocking DNA damage in active genes is repaired by transcription-coupled NER (TCR). There are two autosomal recessive disorders that are specifically deficient in TCR : Cockayne syndrome (CS) and UV-sensitive syndrome (UV^sS). CS is characterized by photosensitivity and abnormal physical and neurological development. On the other hand, UV^sS patients show photosensitivity and mild freckling with no skin tumors. In this study, molecular mechanism of TCR and molecular pathogenesis of XP, CS and UV^sS have been analyzed.