Déficiences de l'acide désoxyribonuclèique et métabolisme cellulaire

Abstract

The present paper attempts to compare in different types of organisms how DNA deficiency (obtained by deprivation of an essential precursor, by irradiation or intoxication, or by total enucleation) can affect various cellular processes. Energy-producing mechanisms, (a) Oxidative phosphorylations: mitochondria appear to act independently of the cell nucleus because neither u.v. irradiation (in bacteria), intoxication by nitrogen mustards in embryos or total enucleation in amoebae inhibit the formation of ATP even after long periods of time. One must, however, remember that a genetical control does exist, as demonstrated in yeasts by Ephrussi (1953). The role of DNA in nuclear phosphorylations (MiRSKY et al., 1956) remains very puzzling, because DNA can be replaced by several unspecific polyelectrolytes. (b) Anaerobic phosphorylations, however seem to be much more dependent on nuclear function in the same types of cells; in anucleate amoebae, glycogenolysis is also inhibited. The role of the nucleus in these processes has, however, not been clarified; but, as certain stages of coenzyme I (DPN) synthesis take place in the nucleus, this synthesis might be closely correlated to DNA integrity. Ribonucleic acid and protein synthesis. It is known that the nucleolus is an important site of RNA metabolism and probably synthesis, and RNA could be formed in the nucleolar organizer or in the puffs one observes in certain bands of the chromosomes of larvae of diptera, where Ficq and Pavan (1957) have shown an important RNA and protein metabolism besides active DNA synthesis. In the case of amoebae, the experiments of Goldstein and Plaut have demonstrated a migration of nuclear RNA into the cytoplasm; but, the fact that non-nucleated cytoplasm is still capable of incorporating low molecular precursors into RNA, despite a rapid loss of total RNA, demonstrates that cytoplasmic RNA is capable of being metabolized in the absence of a nucleus; and, in non-nucleated acetabularia, a net synthesis has even been observed under certain conditions. One is therefore led to postulate a certain degree of independency of cytoplasmic RNA metabolism, although the nucleus seems to control the maintenance of cytoplasmic RNA. Similar observations on protein synthesis have been made in acetabularia where important increases of total protein and of certain enzymes have been observed during growth of the non-nucleated half. The non-nucleated halves are even still capable of cellular differentiation, but this is only possible for a certain time because, if they are kept in the dark for 2 or 3 weeks after enucleation, they lose their capacity of forming their differentiated cap. In micro-organisms, DNA can be destroyed by X-irradiation, but there is no immediate loss of the capacity to form induced enzymes; this has been clearly demonstrated by Chantrenne and Devreux (1958). Embryos containing abnormal DNA are capable of cleaving apparently normally and of incorporating high amounts of amino acids into their proteins, but they become incapable of differentiation. One is led to postulate a certain independency from the nucleus of RNA and protein synthesis and, in certain extreme cases, one has suggested that this independency might be total as in cytoplasmic heredity. The complicated pathway by which genetic information proceeds before becoming expressed in the cytoplasm by the synthesis of specific constituents explains that the deficiency in DNA does not immediately stop specific protein synthesis; but, if DNA has been affected for some time (as in the case of the embryos containing abnormal DNA or acetabularia which has been kept in the dark), differentiation will no more be possible. Mitotic processes. In micro-organisms, a deficiency of DNA-forming precursors arrests both nuclear and cytoplasmic divisions; but cell division can also be inhibited in conditions where [DNA synthesis appears to proceed normally, as in many irradiation experiments ; and one knows of several instances of cytoplasmic cleavage in enucleated embryos. One is therefore led to conclude that cell constituents other than DNA also play an important part in controlling mitotic processes.