College of Letters Arts & Sciences
DNA Methylation, Mutagenesis and Evolution
The mechanisms of mutation "hot" and "cold" spots are being investigated in relation to evolution. We examine nearest-neighbor influences on point mutations arising through DNA polymerases and DNA methylases. in vitro experiments with prokaryotic and eukaryotic DNA polymerases show S1-nearest neighbor influences on error rates that may be related to base-stacking interactions. Vertebrates have a nuclear DNA C-methylase that promotes C--T mutations in CG sites, causing CG to be replaced by TG or CA everywhere in nuclear DNA except in short regions called "CpG islands." Recently we have obtained evidence such regions are kept mutationally "cold" by the binding of zinc-finger Sp 1, a common transcription factor that recognizes GGGCGGG and interacts with other factors. The consequences of CG replacements by TG or CA and their suppression are being examined in relation to the protein genetic code.