Figure 1.

Fate of O⁶-alkyl G adducts in AGT-deficient cells (G:C→A:T transition mutations). In AGT-proficient cells, the O⁶-alkyl adduct is removed from G through direct transfer to an acceptor protein. In AGT-deficient cells, there are two possible fates for this and similar adducts. If the cellular DNA is replicated, the O⁶-alkyl G is misreplicated as an A and a T is incorporated in the new DNA strand. Subsequent replication “fixes” the G:C→A:T mutation (A, mutation in red). This would yield a colony of 50% mutant cells. In the absence of DNA replication, nucleotide excision repair (NER) or base excision repair (BER) processes might recognize the “mismatched” base pair. Correct repair would remove the O⁶-alkyl G and insert the correct G. Misrepair would remove the C and insert a T opposite O⁶-alkyl G. The now fixed G:C→A:T mutation would be propagated during subsequent DNA replication (B, mutation in red). The total mutant yield through misrepair would be the same, assuming a 50% probability of either repair or misrepair. However, the mutant colony would be “pure,” i.e., 100% mutant cells.