IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 189 



of the chromatin in the process of being synthesized is extremely small 

 compared to that which is either already synthesized completely or that 

 which is not yet synthesized. Thus, only a small portion of the material 

 is being replicated at any time (Sueoka, 1960; Meselson and Stahl, 

 1958). Whether this portion moves from one end of the chromatid to 

 the other is not known. That this may be the case is indicated indirectly 

 by the experiments of Rudner (1960) on the induction of mutations by 

 2-aminopurine incorporated into a synchronized culture of bacteria. In 

 this case, appearance of mutants occurred in steps, whereas DNA was 

 synthesized continuously. This would indicate that synthesis of particu- 

 lar loci in the DNA molecule occurred at precisely timed intervals. 



It is difficult to see how sequential synthesis of DNA can be avoided 

 if strand separation is to occur without frequent breakage or crossing 

 over which would destroy the semi-conservative pattern of chromosome 

 duplication which has often been observed. If DNA synthesis occurs in 

 small bursts covering the rapid synthesis of one segment (molecular 

 weight ca. 10") after another of the chromatid and if these are to be 

 stabilized bj^ linkers of some type, it also would appear reasonable to 

 suppose that a stabilized type of bonding (perhaps covalent) must occur 

 at each end of the segment, to prevent subsequent rupture of terminal 

 hydrogen bonds and possible loss of the semi-conservative pattern. Such 

 bonding has been shown to result from ultraviolet irradiation and it is 

 possible that it could occur in the absence of irradiation. If this were 

 the case, initiation of synthesis could be an all-or-none event dependent 

 upon breakage of such critical bonds (Marmur and Grossman, 1961). 



A key question concerning control via a point of initiation may be: 

 What happens to cells in wdiich DNA synthesis is interrupted before 

 completion? When synthesis is resumed will it resume at the point of 

 the chromatid where it was interrupted, or at the original initiation 

 point? We do not know whether, once initiated, the conditions necessary 

 for DNA synthesis remain imposed upon the cell until such synthesis 

 can be completed. To study this, it is necessary to have a system in 

 which damage to DNA or other cell constituents does not occur during 

 the blockage of synthesis. The use of deoxyadenosine inhibition for 

 autoradiographic studies of chromosome synthesis in higher cells would 

 appear extremely fruitful from this point of view. 



In general, it is obvious that if DNA synthesis is initiated at one end 

 of the molecule, special conditions will be needed to distinguish the 

 beginning and end of the molecule and to jirepare it for initiation of 

 synthesis. 



Such a statement implies that the molecule itself carries specific 

 information which differentiates one end from the other. If this dif- 



