Analysis of Models Involving Enzymatic Activities for the Occurrence of C→T Transition Mutations During Repeat-Induced Point Mutation (RIP) inNeurospora crassa

Abstract The phenomenon of repeat-induced point mutation (RIP), acting during the sexual phase of the model eukaryote Neurospora crassa , is considered to study the putative in vivo relationships existing between cellular levels of S-adenosylmethionine (SAM), cytosine methylation and the occurrence of C→T transition mutations. We analyse the kinetic behaviour of the different enzymatic models proposed to explain the underlying mutagenic mechanisms of RIP. The dependence of the mutation rate on the cellular levels of the methyl group donor SAM was evaluated for the models of mutation catalysed by a DNA-cytosine deaminase, a DNA-(5-methylcytosine) deaminase, a DNA-(5-cytosine) methyltransferase, and for a model combining the activities of the last two enzymes. We propose that these models can be distinguished by studying the dependence of RIP on intracellular SAM levels.