Abstract
BackgroundAbasic sites are formed spontaneously and by nucleobase chemical modifications and base excision repair. A chemically stable abasic site analog was site-specifically introduced into replicable plasmid DNAs, which were transfected into human U2OS cells. The amplified DNAs were recovered from the cells and used for the transformation of a bacterial indicator strain.ResultsLarge deletion mutations were induced by the analog, in addition to point mutations at the modified site. No apparent sequence homology at the deletion junctions was found.ConclusionThese results suggested that the large deletions induced by the abasic site analog are formed by homology-independent events.
Highlights
Abasic sites are formed spontaneously and by nucleobase chemical modifications and base excision repair
An abasic site is formed by the spontaneous hydrolysis of the N-glycosyl bonds of DNA, and this hydrolysis is accelerated by the chemical modifications of bases [6]
We focused on deletion mutations upon the transfection of a shuttle plasmid DNA bearing a chemically stable, frequently used tetrahydrofuran analog (THF) of the abasic site
Summary
Chemical modifications of nucleic acids have severe effects on organisms because they disturb replication, transcription, and translation, resulting in mutagenesis, carcinogenesis, and cell death. An abasic (apurinic/apyrimidinic, AP) site is formed by the spontaneous hydrolysis of the N-glycosyl bonds of DNA, and this hydrolysis is accelerated by the chemical modifications of bases [6]. Large deletion mutations were found when shuttle vectors containing ultraviolet-induced DNA lesions, cyclobutane and 6–4 thymine-thymine dimers, were replicated in simian cells [16]. Since these dimers block nucleotide incorporation by replicative DNA pols as with the abasic site [17], it may cause large deletion mutations in addition to point mutations. The analog caused large deletion mutations in living human cells, without any apparent homology at the deletion junctions
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