96 



MUTATIONS 



2-aminopurine 

 (normal amino- state) 



5-hydroxymethyl cytosine 

 (normal amino-stote) 



Figure 19. 



2-aminopurine. Normally it should be able to pair at these two 

 positions with thymine. The two hydrogen-bonds are the same as 

 one observes in the pairing between guanine and cytosine; so, again, 

 the distances and angles should be proper to allow pairing. 



The question was why is 2-aminopurine so much more mutagenic 

 than 5-bromouracil with so little 2-aminopurine incorporated. 



Auerbach: About 3000 times as much, from what you say. 



Freese: Yes. The explanation is given in Figure 19. While bromoura- 

 cil can make a mistake and pair with guanine only after it has lost 

 one hydrogen, as I showed before, 2-aminopurine can make one hydro- 

 gen bond when both of the molecules, aminopurine and cytosine, are 

 in their normal tautomeric state; in other words, this one hydrogen 

 bonding should occur as frequently as the two hydrogen bondings 

 which 2-aminopurine makes with thymine. The only difference is that 

 this bond does not force the base pair into the right distance and angle, 

 but the base can swing about. Occasionally, however, the base will 

 have the right distance and can get incorporated into DNA. The 

 frequency with which this occurs should be much higher than the fre- 

 quency with which a tautomeric shift occurs for 5-bromouracil. 



Auerbach: Can you estimate the probability for aminopurine? 



Freese: No. The argument is the following: The frequency of tauto- 



