THE CENTRAL PROBLEMS OF THE BIOCHEMISTRY OF CELL DIVISION 477 



evidence that DNA synthesis may be continuous during the hfe cycle of 

 bacteria creates no paradox ; it may merely be telling us that the bacterial 

 genetic apparatus is not required to go through a mitotic cycle. 



I know of no reasonable speculation to account for the fact that DNA 

 in cells of higher organisms only doubles, after which synthesis ceases until 

 the cell has divided. If such a limitation is not inherent in the enzyme 

 system it may be referable to chromosomal organization, which will be 

 considered next. 



2. Reproduction of the chromosomes 



Even if one regards the chromosome genetically as a package of DNA, 

 the problems of cell division draw our attention to packing as well as to its 

 contents, and even to the handles by which it is carried. No one doubts 

 that the chromosome is not only large, but also chemically complex. It 

 contains at least as much protein as DNA, and lipids and RNA have also 

 been included in estimates of its composition. 



Some fundamental questions concerning the chemical structure of 

 chromosomes have been under study for 20 years or more without being 

 resolved. One such question, rephrased in contemporary form, is whether 

 a single chromosome can be viewed as an enormously extended DNA 

 molecule. Such a state of affairs would greatly simplify the theoretical 

 structure of genetics, for it would abolish an otherwise necessary distinction 

 between coarse and fine-structural genetic phenomena, and would tend 

 to validate the phage or the bacterial chromosome as a general genetic 

 model. Experimentally, the question takes this form: is the chromosome a 

 DNA continuum to which discrete protein units are attached (cf. [4]), 

 a protein continuum to which discrete DNA units are attached (cf. [5, 6]), 

 an assembly of nucleoprotein macromolecules which are linked to each 

 other by bonds weaker than covalent bonds (cf. [7]), or is it composed of 

 alternating segments of DNA and protein ? Unfortunately, there is 

 plausible evidence for all of these views. Quite apart from the elegancies 

 of genetic theory, we need a decisi\e answer to this simple question 

 before we can make a pointed attack on chromosome heliaviour in cell 

 division. 



A second question concerning the complexity of the chromosomes 

 concerns their fundamental multiplicity. To what extent are they composed 

 of bundles of genetically identical units, representing redundancy of genetic 

 information. 



Thus far, each method of attack on the question leads to a different 

 answer. The geneticists prefer that each chromosome be a single element, 

 for if it is a bundle of identical elements the interpretation of mutation 

 becomes difficult in a number of ways. The cytologists and the students 

 of chromosome breakage have preferred a two-imit chromosome and can 



