DNA repair excision nuclease attacks undamaged DNA - A potential source ofspontaneous mutations

Nucleotide excision repair is a general repair system that eliminates many dissimilar lesions from DNA. In an effort to understand substrate determina nts of this repair system, we tested DNAs with minor backbone modifications using the ultrasensitive excision assay. We found that a phosphorothioate and a methylphosphonate were excised with low efficiency. Surprisingly, we also found that fragments of 23-28 nucleotides and of 12-13 nucleotides cha racteristic of human and Escherichia coli excision repair, respectively, we re removed from undamaged DNA at a significant rate. Considering the relati ve abundance of undamaged DNA in comparison to damaged DNA in the course of the life of an organism, we conclude that, in general, excision from and r esynthesis of undamaged DNA may exceed the excision and resynthesis caused by DNA damage. As resynthesis is invariably associated with mutations, we p ropose that gratuitous repair may be an important source of spontaneous mut ations.