Heterogeneity of DNA Repair in Relation to Chromatin Structure
Analysis of repair processes in mammalian cells has largely been focused on induction and repair of DNA damage in the genome overall. In particular the repair of ultraviolet light-induced photoproducts has been intensively studied in a variety of mammalian cells and in most cases UV-induced cytotoxicity can be correlated to the extent of unscheduled DNA synthesis or removal of pyrimidine dimers from the nuclear DNA. For example variation in UV-induced cytotoxicity found both within and between the various complementation groups of the human UV-sensitive disorder xeroderma pigmentosum (XP) generally correlates with the extent of defective excision repair (Kantor and Hull 1984). However, a notable exception to this is found in nondividing XP-cells belonging to complementation group C, which are relatively resistant to the lethal effects of UV (Kantor and Hull 1984; Mayne and Lehmann 1982). Also, in a number of other cases the removal of pyrimidine dimers from the genome overall turned out to be an invalid parameter to predict UV-induced cytotoxicity. Cockayne’s syndrome (CS) is a human disorder characterized at the cellular level by an increased sensitivity to the killing effects of UV-light, but with an apparently normal capacity to perform unscheduled DNA synthesis or to remove pyrimidine dimers (Mayne and Lehmann 1982). The various rodent cell lines consistently exhibit low levels of pyrimidine dimer removal for the genome overall (Van Zeeland et al. 1981) but are equally resistant to lethal effects of UV-light as human cells which are capable of performing fast and efficient repair of pyrimidine dimers.
KeywordsToxicity Sucrose Lithium Cage Sedimentation
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