Abstract
APURINIC sites in cellular DNA may occur secondary to the slow hydrolysis of purines in physiological conditions1 or the rapid hydrolysis of alkylated purines2. Endonucleases which incise double-stranded DNA at apurinic sites have been purified from E. coli3, calf thymus4 and rat liver5. It has been proposed that such endonucleases hydrolyse the apurinic site as the first step of a repair process similar to excision-repair of ultraviolet photoproducts6. Lindahl and Nyberg calculated that spontaneous depurination, if unrepaired in postmitotic cells such as human neurones, would result in the loss of 3% of the total purines during a lifetime1. Such a loss could be sufficient to produce abnormal proteins which appear in ageing cells7. The more rapid depurination of alkylated bases could be related to the mutagenic and carcinogenic properties of alkylating agents8. Therefore, to relate the repair of apurinic sites to the pathogenesis of human disease, we have characterised the properties of apurinic site endonuclease activity in crude extracts of HeLa cells and then measured such activity in WI-38 cells and human skin fibroblasts. We then compared enzyme activity in skin fibroblasts from individuals with two diseases in which repair of apurinic sites might be defective—progeria, characterised by premature ageing9 and associated with abnormal thermolability of cellular enzymes10, and Fanconi's anaemia, associated with an increased incidence of malignancy and in vitro susceptibility to chromosome breakage by alkylating agents11.
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TEEBOR, G., DUKER, N. Human endonuclease activity for DNA apurinic sites. Nature 258, 544–547 (1975). https://doi.org/10.1038/258544a0
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DOI: https://doi.org/10.1038/258544a0
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