title: Binding specificities of the mismatch binding protein, MutS, to oligonucleotides containing modified bases.
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.
authors.affiliation: Gene Research Center, Okayama University.
authors.forename: K
authors.initials: K
authors.lastname: Negishi
authors.forename: D
authors.initials: D
authors.lastname: Maehara
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: D
authors.initials: D
authors.lastname: Loakes
authors.forename: L
authors.initials: L
authors.lastname: Worth
authors.forename: R M
authors.initials: RM
authors.lastname: Schaaper
authors.forename: K
authors.initials: K
authors.lastname: Seio
authors.forename: M
authors.initials: M
authors.lastname: Sekine
authors.forename: T
authors.initials: T
authors.lastname: Negishi
mesh_terms: D015075:2-Aminopurine / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins; D020137:Base Pair Mismatch; D001483:Base Sequence; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D004268:DNA-Binding Proteins; D003853:Deoxyribonucleosides / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000378:metabolism*; D051719:MutS DNA Mismatch-Binding Protein; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry* / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C115248:2'-deoxy-ribofuranosyl-(3,4-dihydro-6H,8H-pyrimido(4,5-c)(1,2)oxazin-7-one); D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D003853:Deoxyribonucleosides; D029968:Escherichia coli Proteins; D009692:Nucleic Acid Heteroduplexes; D009841:Oligonucleotides; D015075:2-Aminopurine; C038769:N(4)-aminocytidine; D003562:Cytidine; C010737:N(4)-hydroxycytidine; D000251:Adenosine Triphosphatases; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli