476 DANIEL MAZIA 



It is demonstrable, in a sufficiently lengthy treatise on cell division (cf. 

 [2]), that the problems of cell division are linked in some way to almost all 

 of the biochemical problems of the cell, yet certain events may be regarded 

 as being specifically related to division. Some of these have been partly 

 amenable to biochemical attack or speculation, and these will be outlined. 



I. DNA synthesis 



So far as we know, the life of an individual cell does not depend on 

 continued synthesis of DNA. With some exceptions that should not be 

 ignored (cf. [3]), the doubling of DNA may be regarded as a preparation 

 for division. One of the truly important discoveries of modern cyto- 

 chemistry has been the demonstration that DNA synthesis — in cells that 

 divide by mitosis, which includes all plant and animal cells- takes place 

 between divisions, in anticipation of division, and not during the mitotic 

 period. In differentiated multicellular organisms, certain categories of cells 

 do not divide, and these generally do not synthesize DNA, but retain the 

 DNA received from the division at which they arose. Since many such 

 cells can be made to synthesize DNA and to divide under carcinogenic 

 influences or merely by removing them from the organism, their failure to 

 synthesize DNA can be viewed as an inhibition imposed by their environ- 

 ment. If DNA synthesis takes place at all, it generally goes all the way to a 

 doubling of the original amount. In a larger view, the "regulation" or 

 " control " in the sense of a modulation of time or rate or ultimate amount 

 synthesized is not a serious problem for the present. The questions of 

 "control" are: (i) How can DNA synthesis be totally suppressed by a 

 great variety of organismal factors ; hormones, immunity factors, etc. ; and 

 (2) why does it stop when the original dose of DNA has just doubled ? 

 The first question, one predicts, will be solved as a straightforward though 

 profound biochemical problem, involving such variables as the induction 

 of the polymerizing enzyme or of enzymes providing the nucleotide pre- 

 cursors or in terms of direct inhibition of the enzymes assuming that they 

 are always present. There are, however, structural factors of major 

 importance. These express themselves in the fact that DNA synthesis, in 

 cells of higher organisms can take place only during the phase of the cell 

 cycle from telophase to the next prophase, when the chromosomes are so 

 thoroughly extended or uncoiled that they are not resolvable with the 

 microscope. It cannot take place during the mitotic period when the 

 chromosomes are coiled into the compact packages by which we recognize 

 them. The condensation of the chromosomes for mitosis is intelligible in 

 terms of the requirements for moving them about. The fact that this 

 condition is incompatible with DNA synthesis explains the discontinuity 

 of such synthesis in the life-history of cells of higher organisms. The recent 



