Repair of 8-hydroxyguanine in DNA by mammalian N-methylpurine-DNA glycosylase.

Abstract

8-Hydroxyguanine is one of the major base lesions implicated in mutagenesis induced by ionizing radiation and radiomimetic agents. This lesion appears to be repaired by human cells via multiple pathways including the one that involves a base glycosylase. Mouse N-methylpurine-DNA glycosylase, responsible for the removal of N-alkylpurines in DNA that are induced by simple monofunctional alkylating agents, also releases 8-hydroxyguanine from DNA in vitro and in vivo in Escherichia coli. The human N-methylpurine-DNA glycosylase, with a lower preference for N-alkylguanine than the mouse protein, removes the oxidized base less efficiently than the mouse protein. The recombinant mammalian glycosylases can rescue E. coli lacking MutM (Fpg) protein, the DNA glycosylase that is primarily responsible for removing 8-hydroxyguanine from the bacterial DNA.