39 l 



CHAPTER 31 



Uracil 



OH 



O^N- 

 H 



Adenine 



i k.i kf, 31-2. Tautomers of uracil and adenine. 



of the already-formed, "old" gene material. 

 Single, whole-nucleotide changes can also be 

 produced by chemical mutagens without in- 

 volving breakage. Molecules of chemical 

 mutagens such as the acridities (Figure 

 31-1) can be inserted between successive 

 nucleotides of a strand. 1 ' A single, inter- 

 calated molecule of chemical mutagen is 

 apparently able to spread the strand length- 

 wise 3.4A. When this chain is used as tem- 

 plate, an entire nucleotide may be added to 

 the complementary chain at the position oc- 

 cupied by the molecule of mutagen. The 

 possibility also exists that an unbound nu- 

 cleotide or other naturally-occurring sub- 

 stance may intercalate with similar results. 

 This mutagenic mechanism involves changes 

 both in the old and the new DNA strands. 



In the presence of Mn , the comple- 

 mentary strand made by DNA polymerase 

 from a DNA template in vitro is a mixture 

 of deoxyribo- and ribotides, 7 provided, of 

 course, that the appropriate riboside 5' tri- 



5 See H. Harrington (1964). and C. G. Mead 

 (1964). 



y See L. S. Lerman (1963 J. 



' As shown by P. Berg and co-workers (see refer- 

 ence on p. 290). 



phosphates are included as substrates. The 

 incorporation of U and ribose into a comple- 

 mentary strand is expected to be mutational. 

 Since salts of manganese are highly muta- 

 genic in bacteria, 8 it appears that such an 

 incorporation may occur in vivo. 



Sub-Nucleotide Mutations 



Mutation can involve the sugar, phosphate, 

 or base portions of a nucleotide. Although 

 deoxyribose is the only sugar detected in the 

 DNA of microorganisms, one cannot ex- 

 clude the possibility that an occasional ribose 

 occurs in an otherwise typical DNA strand. 

 Ribose can be part of a DNA chain synthe- 

 sized in vitro if whole ribotides are incorpo- 

 rated by the method described in the pre- 

 ceding paragraph. Some evidence has been 

 obtained for the incorporation of arabinose 

 into DNA of mammalian cells in culture. 

 As mentioned, ribosides give no evidence of 

 acting as DNA mutagens; in fact, purine 

 ribosides are sometimes antimutagenic. 

 Nevertheless, we cannot rule out the possi- 

 bility that some agents act as mutagens either 

 by adding an O at the 2' position of deoxy- 

 ribose in an already-formed DNA sequence 



H As shown by M. Demerec and co-workers. 



