Weak to severe deficit of GATC sequences in the DNA of enterobacteriophages 
appears to be correlated with their undermethylation during growth in dam+ (GATC 
ade-methylase) bacteria. This observation is corroborated by the sequence 
analysis showing no evidence for site-specific mutagenicity of 6meAde. The MutH 
protein of the methyl-directed mismatch repair system recognizes and cleaves the 
undermethylated GATC sequences in the course of mismatch repair. To enquire 
whether the MutH function of the methyl-directed mismatch repair system 
participates in counterselection of GATC sequences in enterobacteriophages, we 
have studied the yield of bacteriophage phi X174 containing either 0, 1, or 2 
GATC sequences, in wild type, dam, and mut (H, L, S, U) Escherichia coli. 
Following transfection with unmethylated DNA containing two GATC sequences, a 
net decrease in the yield of infective particles was observed in all bacterial 
mutH+ dam- strains, whereas no detectable decrease was observed in bacteria 
infected by DNA without GATC sequence. This effect of the MutH function is 
maximum in wild type and mutL and mutS bacteria whereas the effect is not 
significant in mutU bacteria, suggesting an interaction of the helicase II with 
the MutH protein. However, in dam+ bacteria, the presence of GATC sequences 
leads to an increased yield of infective particles. The effect of GATC sequence 
and its Dam methylation system on phage yield in mutH- bacteria reveals that 
methylated GATC sequences are advantageous to the phage.(ABSTRACT TRUNCATED AT 
250 WORDS)