title: [Role of tautomerism in the molecular mechanisms of mutagenesis].
abstract: Environment of human being usually contains a high number of environmental mutagens, which may modify chemically nucleic acid bases into promutagenic analogues. Hydroxylamine (NH2OH) is a strong mutagen which modifies cytosine and adenine to N4-hydroxycytosine and N6-hydroxyadenine, respectively. Once these analogues are present in DNA or RNA, they may cause transition point mutations by the exchange between two pairs C:G and A:T into T:A and G:C, respectively. The reason for these mutations is the change of preferences between intermolecular hydrogen bonds resulting from the shift of the tautomeric equilibrium from the preferred amino form into the imino one. In the case of the amino<-->imino tautomeric equilibrium of N6-hydroxyadenosine, it was also shown that preferential hydrogen bonding between its imino form and cytidine, or uridine and the amino form of this base leads to the shift of the tautomeric equilibrium in favour of these tautomers in solution. N4-hydroxy-dCMP analogues exhibited very interesting inhibitory properties versus the biosynthesis of dTMP catalyzed by thymidylate synthase. These properties help to further the knowledge on the molecular mechanism of the catalytic reaction of this enzyme as well as on the role of syn-anti photoisomerization of the N4-hydroxy group in this reaction. Examinations gathered in the article were conducted from 1979 to 1985 under supervision, and afterwards from 1986 to 2004 in collaboration with professor David Shugar.
authors.forename: Borys
authors.initials: B
authors.lastname: Kierdaszuk
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000266:history / Q000378:metabolism; D020029:Base Pairing; D001671:Biochemistry / Q000266:history*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000266:history / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000266:history; D004249:DNA Damage; D005823:Genetics / Q000266:history*; D049673:History, 20th Century; D049674:History, 21st Century; D006860:Hydrogen Bonding; D007536:Isomerism; D016296:Mutagenesis; D017354:Point Mutation; D011044:Poland
chemical_list: C021202:N(4)-hydroxycytosine; C032610:6-N-hydroxylaminopurine; D003596:Cytosine; D004247:DNA; D000225:Adenine