BASE PAIRING AND MUTAGENESIS

City Of Hope/Beckman Research Institute, Duarte CA

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Abstract

DESCRIPTION: This is a competitive continuation of a R29 grant which was awarded in 1988. The focus of the work is the study of mutagenesis by a combination of organic chemistry, NMR, and in vitro polymerase methods. The specific aims are to: 1) study the equilibrium between H-bonding patterns for 5-Br-dU and 2-amino-dpurine at a replication fork model, employing NMR methods. 2) use NMR to study the pseudorotational state of bases at the 3' terminus of a primer strand, at an in vitro model of a replication fork. 3) use NMR to study the equilibrium between syn and anti forms of exocyclic alkyl groups on dG (O6-methyl dG) and dA (N6- methyl dA), again with the replication fork model. 4) use NMR, optical methods and in vitro replication methods to study the mechanism of the high mutational efficiency of 5-OHdC. The modified base will be positioned internal to a blunt ended duplex, rather than in the replication fork model. 5) to use NMR to study the structure of N3- hydroxyalkyl derivatives of dU. The modified base will be positioned internal to a blunt ended duplex, rather than in the replication fork model.