DNA MISMATCH REPAIR AND DNA METHYLATION IN ADULT BRAIN NEURONS

DNA repair is essential for maintaining the integrity of the nucleotid e sequence of cellular DNA over time. Although much information has ac cumulated recently on the mechanisms of DNA repair in cultured cells, little is known about the DNA repair capabilities of cells in the adul t brain. In the present study, we have investigated the capacity of nu clear extracts from adult rodent brain neurons to carry out DNA mismat ch repair. We focused on the repair of G . T and G . U mismatches, whi ch are caused by deamination of 5-methyl cytosine to thymine, or cytos ine to uracil, respectively, because these are the only types of misma tches that can arise in nondividing cells. We found that nuclear extra cts from adult brain neurons can correct G . T and G . U mismatches, r estoring them to G:C base pairs. Several other types of DNA mismatches could not be processed. These data provide the first direct demonstra tion that neurons in the adult mammalian brain have the capability to carry out DNA mismatch repair. We also we report that adult brain cont ains high levels of DNA methyltransferase (MTase) activity. We propose that one function of DNA MTase in the adult brain is to remethylate n ewly incorporated cytosine residues from G . T mismatch repair after d eamination of 5-methyl cytosine, thereby maintaining the original patt ern of DNA methylation. The high levels of brain DNA MTase suggest fur ther that this enzyme has additional functions in the brain.