IV. CELLILAR CONTROL OF DNA BIOSYNTHESIS 187 



evidence has been obtained which indicates that heat-denatured DNA, 

 which will act as primer in self-replication, is unable to function in the 

 in vitro synthesis of messenger RNA (Burma et al., 1961 ; Ochoa et al., 

 1961; Eisenstadt et al, 1962). 



That DNA and RNA synthesis are mutually exclusive in vivo is 

 indicated by the experiments of Sisken (1959) and of Prescott and 

 Kimball (1961). The latter workers studied the synthesis of RNA, DNA, 

 and protein in the macronucleus of the ciliate Euplotes. As mentioned 

 previously, DNA synthesis in this case proceeds via a DNA-synthesizing 

 band, commencing at the edge of each lobe of the U-shaped macronucleus 

 and continuing until the two bands meet (Gall, 1959). The nucleus then 

 divides. They demonstrated that this DNA-synthesizing band is devoid 

 of RNA and incapable of synthesizing RNA. It is only this part of the 

 nucleus which was shown to have these two characteristics. Whether 

 the progression of the synthesizing band is responsible for the cessation 

 of RNA synthesis and dissociation of RNA-DNA complexes, or the 

 result of it, is not known. It is obvious that if the latter were true, dis- 

 sociation of the RNA-DNA complex and cessation of RNA synthesis 

 could be a controlling factor in DNA synthesis. 



Such a mechanism could explain the observed dependence of DNA 

 synthesis on the ability of cells to carry on RNA synthesis (see Section 

 III) since RNA synthesis could be blocked in such a way as to prevent 

 dissociation of a DNA-RNA complex, or to favor reassociation. The 

 recent findings of Aronson and Spicgelman ( 1961a, b) would indicate that 

 chloramphenicol might, under certain conditions, create a situation in 

 which this could occur. The formation under these conditions of RNx\- 

 DNA complexes could also explain the reduction of ultraviolet-induced 

 mutation.-^ which occurs in the absence of RNA synthesis (Witkin, 1959; 

 Doudney and Haas, 1961), since complex formation with RNA and 

 subsequent lack of DNA replication might help to stabilize the structure 

 of DNA until ultraviolet-induced lesions could be repaired. On the other 

 hand, mutations induced by a change in base structure (resulting from 

 alkylating agents) should not be affected, as is indeed the case (Strauss 

 and Okuba, 1960). Finally, the observed dependence of "thymineless 

 death"« (Gallant and Suskind, 1961, 1962) and DNA synthesis (Kellen- 

 berger et al, 1962) on conditions leading to RNA synthesis could also be 

 explained as a stabilization of DNA (which had undergone lesions as 

 the result of attempted synthesis in the absence of thymine) by complex- 

 ing with RNA. In all of these situations, RNA synthesis may be 

 visualized as resulting in a turnover, and therefore dissociation, of RNA- 



* This occurs when bacteria which require thymine for growth are incubated in 

 media lacking thymine. 



