O(6)-alkylG adducts are highly mutagenic due to their capacity to efficiently 
form O(6)-alkylG:T mispairs during replication, thus triggering G→A transitions. 
Mutagenesis is largely prevented by repair strategies such as reversal by 
alkyltransferases or excision by nucleotide excision repair (NER). Moreover, 
methyl-directed mismatch repair (MMR) is known to trigger sensitivity to 
methylating agents via a mechanism that involves recognition by MutS of the 
O(6)-mG:T replication intermediates. We wanted to investigate the mechanism by 
which MMR controls the genotoxicity of environmentally relevant O(6)-alkylG 
adducts formed by ethylene oxide and propylene oxide. Recently, the 
alkyltransferase-like gene ybaZ (eATL) was shown to enhance repair of these 
slightly larger O(6)-alkylG adducts by NER. We analyzed the toxicity and 
mutagenesis induced by these O(6)-alkylG adducts using single-adducted plasmid 
probes. We show that the eATL gene product prevents MMR-mediated attack of the 
O(6)-alkylG:T replication intermediate for the larger alkyl groups but not for 
methyl. In vivo data are compatible with the occurrence of repeated cycles of 
MMR attack of the O(6)-alkylG:T intermediate. In addition, in vitro, the eATL 
protein efficiently prevents binding of MutS to the O(6)-alkylG:T mispairs 
formed by the larger alkyl groups but not by methyl. In conclusion, eATL not 
only enhances the efficiency of repair of these larger adducts by NER, it also 
shields these adducts from MMR-mediated toxicity.