396 



( II M'TF.R 31 



mutagens. Nitrous acid (HNO_) is muta- 

 genic tn I \1\ . 12 and 14 phages, bacteria. 

 yeast, and to transforming DNA. This mu- 

 tagen removes NH_. from — that is. deami- 

 nates — purines and pyrimidines both in DNA 

 and RNA. Deaminatcd A becomes hypo- 

 xanthine (Figure 21-4) (which then pairs 

 with C); deaminatcd C becomes U (which 

 then pairs with A): and deaminatcd G be- 

 comes xanthine (which still pairs with C but 

 with only two H bonds). 



Exposure of 4>T4 to low pH induces point 

 mutations. /// vitro, low pH causes depuri- 

 nation — the complete removal of all G and 

 A — which results in apurinic acid. Al- 

 though the backbone of apurinic acid may 

 break after a return to higher pH. it is likely 

 that the point mutations produced in <£T4 

 by low pH are caused either by an incorrect 

 replacement of bases or by the formation of 

 a complement with the complementary nu- 

 cleotide deleted. 



The absorption of ultraviolet (UV) light 

 by nucleic acids depends primarily upon the 

 presence of chromatophoric groups (special 

 groups containing double bonds). When 

 free bases are treated with UV, pyrimidines 

 are found to be more liable to chemical 



change than purines. One common change 

 is the addition of water to the double bond 

 between the number 4 and 5 carbon atoms 

 of pyrimidines. The photoproduct in the 

 case of cytosine is shown in Figure 31-4A. 

 Although the photoproduct reverts to cyto- 

 sine upon heating or acidification, it may 

 persist frequently enough /'// vivo to weaken 

 H-bonding between C and G, thereby lead- 

 ing to localized areas of strand separation or 

 denaturation. Supporting this view is the 

 observation that UV disrupts H-bonding in 

 native double-stranded DNA. 



UV also changes thymine at the same 

 position as cytosine, by breakage of the 

 4-5 double bond; in this case two thymines 

 unite to form a dimer (Figure 31-4B). The 

 UV-initiated hydration of C is expected — via 

 the weakening of H-bonding between C and 

 G — to increase the likelihood of T dimeriza- 

 tion. Thymine dimers form not only be- 

 tween T's on different strands — thereby 

 producing cross links between DNA chains 

 — but also between adjacent T's on the same 

 strand. ( Interchain crosslinking is also pro- 

 duced by the mutagenic antibiotic, mito- 

 mycin C.) Interchain dimerization prevents 

 chain separation and also blocks replication. 



A. 



NH 2 

 N lf" H 



I 



H 

 Cytosine 



NH- 



Photoproduct 



figure 31-4. Effect of ultraviolet light upon 

 DNA pyrimidines. ( The // atoms attached to 

 ring C atoms are shown.) 



O o 



Q A N A H 



N^O 



H H 



Thymine Monomers 



J800A 



UV 



* H— N 



2400A 



\ II 



cr >r ii ii isr x) 



H H 



Thymine Dimer 



