ANALYSIS OF MODELS INVOLVING ENZYMATIC-ACTIVITIES FOR THE OCCURRENCE OF C-]T TRANSITION MUTATIONS DURING REPEAT-INDUCED POINT MUTATION (RIP) IN NEUROSPORA-CRASSA

The phenomenon of repeat-induced point mutation (RIP), acting during t he sexual phase of the model eukaryote Neurospora crassa, is considere d to study the putative in vivo relationships existing between cellula r levels of S-adenosylmethionine (SAM), cytosine methylation and the o ccurrence of C --> T transition mutations. We analyse the kinetic beha viour of the different enzymatic models proposed to explain the underl ying 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 prop ose that these models can be distinguished by studying the dependence of RIP on intracellular SAM levels. (C) 1998 Academic Press Limited.