Non-canonical hydrogen bonds in genetic information flow

Abstract

Non-Watson-Crick-type hydrogen bonds involving minor nucleosides such as inosine in anticodon loops of transfer RNA are found in nucleic acids. Inosine contains hypoxanthine as a nucleobase and can form base pairs with various bases in the genetic decoding process. This property was applied to cloning complementary DNA by using oligodeoxyribonucleotide primers which contain deoxyinosine residues. Hypoxanthine is generated by deamination of adenine, one of the major nucleobases in DNA and RNA. Formation of unusual hydrogen bonds derived from damaged nucleobases in nucleic acids is thought to be main cause of disorders in genetic information flow. Mutagenesis and carcinogenesis of damaged bases, including hypoxanthine, 7, 8-dihydro-8-oxoguanine (8-oxoguanine) and pyrimidine photo-dimers in c-Ha-ras genes, were investigated by using synthetic genes containing modified nucleotides. The mode of recognition of unusual base pairing between a thymine photo-dimer and adenine by a repair enzyme was studied by X-ray analysis.



(Communicated by Takashi SUGIMURA, M.J.A.)