PMID:12836344

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Citation

Negishi, K, Maehara, D, Nakamura, S, Loakes, D, Worth, L Jr, Schaaper, RM, Seio, K, Sekine, M and Negishi, T' (2001) Binding specificities of the mismatch binding protein, MutS, to oligonucleotides containing modified bases. Nucleic Acids Res. Suppl. ':221-2

Abstract

We have studied the effects of DNA mismatch repair on mutagenesis induced by nucleoside analogs. Among them, the mutagenic action of 3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one 2'-deoxyriboside (dP) showed high susceptibility to the mismatch repair system, while mutagenesis by N4-aminocytidine and N4-hydroxycytidine was only weakly affected. 2-Aminopurine mutagenesis showed intermediate susceptibility. MutS protein specifically bound to an oligonucleotide duplex containing a dP-dG pair, while the dP-dA pair was bound only weakly. The binding to the dP-dG pair was as strong as binding to a dA-dC mismatch. These specific binding properties can explain the effective avoidance of dP-induced mutagenesis by the mismatch repair system. We have also studied the effects of the repair system on mutagenesis induced by methylating and ethylating agents.

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Keywords

2-Aminopurine/chemistry; Adenosine Triphosphatases/metabolism; Bacterial Proteins; Base Pair Mismatch; Base Sequence; Cytidine/analogs & derivatives; Cytidine/chemistry; DNA-Binding Proteins; Deoxyribonucleosides/chemistry; Escherichia coli Proteins/metabolism; MutS DNA Mismatch-Binding Protein; Nucleic Acid Heteroduplexes/chemistry; Nucleic Acid Heteroduplexes/metabolism; Oligonucleotides/chemistry; Oligonucleotides/metabolism

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