Recombining DNA Damage Repair, Basal Transcription, and Human Syndromes

DNA, the vital carrier of genetic information, is not chemically inert. In the course of time lesions accumulate due to the intrinsic instability of certain chemical bonds. In addition, DNA erodes because of the deleterious effect of numerous exogenous and endogenous genotoxic agents. For instance, the ubiquitous UV component of sunlight induces cyclobutane pyrimidine dimers, 6—4 photoproducts and thymine glycols; X-rays cause various sorts of single strand breaks and the very genotoxic double strand breaks, whereas a wide range of natural and man-made chemicals give rise to many types of DNA adducts, as well as inter- and intra-strand crosslinks (for a review see ref. (5)). Obviously, the corrosion of the double helix interferes with proper functioning, and poses logistic problems for transcription and replication of DNA, which may cause cell death. In addition, DNA lesions frequently give rise to permanent changes in the nucleotide sequence. These mutations can lead to cellular malfunctioning, including carcinogenesis and may contribute to ageing in somatic cells. When occurring in germ cells they may be the cause of inborn genetic defects.