Gene Action — Growth, Differentiation, and Development 



503 



Genetic Regulation of Mitosis 



The genetic control of the structural and 

 physiological features of nuclear and cell 

 division is exemplified in corn and Dro- 

 sophila by mutants which modify spindle 

 shape during meiosis (p. 383) and in a snail 

 by alleles which determine the orientation 

 of the spindle during mitosis. (During snail 

 cleavage, if the spindle becomes oriented one 

 way, a shell with a right-handed coil results; 

 when it becomes oriented the other way, a 

 shell with a left-handed coil is produced.) 

 At present, however, our interest is restricted 

 to the biochemical control of mitosis, espe- 

 cially its genetic basis. 



The microspore of the lily remains in 

 interphase for several weeks. During this 

 time thymidine kinase activity starts at a 

 specific time and lasts no more than 24 

 hours. This observation and others indi- 

 cate 9 that thymidine kinase (needed for 

 DNA replication preceding mitosis) is not 

 always present in the cell but is newly formed 

 for this purpose, and destroyed or inactivated 

 after it has completed its function. This cy- 

 clical behavior system resembles induced en- 

 zyme systems in bacteria (p. 458). Should 

 this system prove representative, it would 

 mean that many of the problems of inter- 

 phase and mitosis concern cyclically-regu- 

 lated gene action. Recall (p. 487), how- 

 ever, that during a cell generation not all 

 gene action is cyclical. 



Viral Regulation of Growth and Differentiation 



Phages regulate the growth and differentia- 

 tion of their bacterial hosts, at least in part, 

 by the messenger RNA produced using the 

 phage genome. In cells infected by virulent 

 T-even phages, the host materials for DNA 

 and protein synthesis are taken over to syn- 

 thesize viral DNA and protein. Temperate 

 phages and various episomes also turn on 



9 See Y. Hotta and H. Stern (1963), and H. Stern 

 and Y. Hotta (1963). 



or off certain of the host's genes, resulting 

 in modification of cellular growth and/or 

 differentiation. Two cancer-inducing viruses, 

 polyoma and SV-40, are each capable of 

 permanently altering the properties of mouse 

 fibroblast cells grown in tissue culture. The 

 characteristics acquired by the virus-infected 

 cells appear to involve latent properties of 

 the cell. For example, infected cells can 

 regain their ability to synthesize collagen 

 suppressed in the uninfected state. We may 

 therefore hypothesize that certain genes are 

 functionally turned on in virus-infected cells, 

 and that the cellular transformations ob- 

 served are functional and not mutational 

 genetic events. 10 



Somatic Cell Mating 



In tissue cultures and sometimes in vivo, 

 successive cell fusions occur between uni- 

 nucleated cells infected with viruses (mea- 

 sles, varicella, herpes, and some mxyo- 

 viruses) and noninfected cells — in a process 

 called polykaryocytosis — to produce giant 

 multinucleated cells which may contain thou- 

 sands of nuclei. These fusions are postu- 

 lated to be associated with an alteration of 

 the cell surface by infecting virus. Poly- 

 karyocytes are characterized by clumped 

 nuclei. 11 



Several mouse tissue culture lines are 

 unique in that each has some chromosomes 

 with a characteristic morphology. After 

 certain pairs of such cell lines are mixed 

 and grown together, uninucleate hybrid cells 

 are produced whose initial chromosome 

 number is approximately the sum of those 

 of the two parent lines and includes chro- 

 mosomes morphologically characteristic of 

 each line. 1 - Over the course of several 

 months, clones of these hybrid cells show 



111 See N. Sueoka and T. Kano-Sueoka (1964), 



and G. J. Todaro, H. Green, and B. D. Goldberg 



(1964). 



"See B. Roizman (1962). 



i-See B. Ephrussi and S. Sorieul (1962). 



