Regulation of Gene Synthesis 



453 



in DNA made under normal conditions no 

 example is known of a usual purine (A or 

 G) being replaced completely or in appre- 

 ciable quantity by another purine. 



Large scale incorporation of 5-bromo 

 uracil, 5-chloro uracil, 5-iodio uracil, 5- 

 fluoro uracil, thiouracil, or 8-azaguanine 

 into DNA may occur when tissue culture 

 cells or bacteria are grown in media con- 

 taining these compounds. Abnormal nutri- 

 tional conditions must be employed to 

 obtain such incorporation, the amount of in- 

 corporation depending partly upon the par- 

 ticular compound under test. Since incor- 

 poration also depends upon the strain tested, 

 this kind of investigation may contribute to 

 our understanding of the genetic control of 

 DNA synthesis. 5-Iododeoxyuridine is in- 

 corporated into the root tip chromosomes 

 of the broad bean plant, Vicia faba. 



A number of analogs of adenosine occur 

 naturally. rt These include a-ribosyl dimeth- 

 ylbenzimidazole, nebularine, psicofuranine, 

 cordycepin, tubercidin, and puromycin ami- 

 nonucleoside. Although some of these com- 

 pounds can be phosphorylated, none has yet 

 been found in either genetic or nongenetic 

 polynucleotides. It would be of great in- 

 terest to know how the cell genetically con- 

 trols the production of these ribosides yet 

 manages to keep them out of nucleic acid 

 polymers. 



It is not too soon to wonder what the 

 genetic basis may be for the amino acid in- 

 terruptions which have been reported to oc- 

 cur periodically along some DNA strands. 

 Such information would be appropriate in 

 the present context, since these interrup- 

 tions may be serving as natural termini for 

 genetic nucleic acid molecules. In vitro, it 

 is possible (p. 289) to add a ribotide to the 

 terminus of a DNA molecule and to syn- 

 thesize a mixed polynucleotide — part DNA 

 and part RNA — using a DNA template and 



e See S. S. Cohen (1963). 



DNA polymerase activated by Mn+ + . Do 

 such reactions take place in vivo? It would 

 be valuable to learn the basis for the regu- 

 lation which results in some mature phage 

 containing double-stranded DNA and other 

 mature phage containing single-stranded 

 DNA. 



Answers to some of these questions may 

 go a long way toward explaining the mech- 

 anism of E. coli chromosome replication. 

 As mentioned on p. 323, the circular E. coli 

 chromosome starts replicating in vivo from 

 a fixed position. Synthesis of the two new 

 strands apparently occurs in parallel; that 

 is, one complement grows at the nucleoside 

 end and the other at the nucleotide end. 7 

 This situation is contrary to the antiparallel 

 synthesis of complementary DNA strands in 

 vitro. A second problem with the in vivo 

 synthesis entails uncoiling. It has been sug- 

 gested that the starting point of DNA syn- 

 thesis serves as a kind of swivel whose rota- 

 tion permits uncoiling. 



Regulation of Synthesis of RNA Genes 



RNA viruses (f2, TMV, poliovirus) serve 

 as messenger RNA to form RNA synthe- 

 tases needed for replication in vivo of com- 

 plementary RNA from RNA. We would 

 like to know if genetic RNA is variable in 

 the respects mentioned for DNA, and to 

 what extent this variability is regulated by 

 the genotype. In this connection we note 

 that poliovirus infection inhibits the syn- 

 thesis of host RNA and induces the synthe- 

 sis of poliovirus RNA that is infectious. 

 Guanidine at concentration 0.001 M inhib- 

 its the synthesis of the latter type of RNA.* 

 After infection with TMV, cytoplasmic ri- 

 bosomal RNA is broken down, and the ri- 

 bosides liberated are utilized in the synthe- 

 sis of TMV-RNA. 9 On the other hand, 

 neither host protein nor host RNA is in- 



7 See J. Cairns (1964). and P. Fong (1964). 



8 See J. J. Holland (1963). 

 ,J See K. K. Reddi (1963). 



