Showing papers in "Annual Review of Biochemistry in 1967"

Deoxyribonucleases: their relationship to deoxyribonucleic acid synthesis.

Abstract: It is likely that nuc1eases and more particularly deoxyribonuc1eases per­ form the degradative function in vivo that they do in vitro. That these en­ zymes may also be involved in some aspects of deoxyribonucleic acid syn­ thesis is less obvious. Nevertheless, there is now evidence, almost all of it circumstantial, which suggests that DNase's may indeed perform some ac­ cessory function in DNA replication. It is the purpose of this review to consider this body of evidence. Support for the notion that DNase's may be involved in DNA synthesis has come essentially from three sources; (a) from in vivo studies with a wide variety of organisms which have shown that cellular DNase levels are gen­ erally, though not invariably, highest during that interval in the growth cycle when DNA synthesis is proceeding at maximal rates; (b) from the appearance, specifically in response to viral infection, of a large number and variety of DNase's ( in certain instances, these enzymes may well func­ tion in the degradation of host DNA to provide the large pool of precur­ sors demanded by the rapid virus-induced synthesis of DNA; on the other hand, virus-specific DNase's, often in high concentration, have been iden­ tified in situations where little if any breakdown of host DNA occurs) ; and (c) from studies of DNA replication by purified DNA polymerases in which it has been observed repeatedly that nucleases can profoundly affect the structure of the template, hence the rate of replication and the nature of the product synthesized. Furthermore, two of the DNA polymerases which have been isolated as physically homogeneous proteins possess exo­ nuclease activity which cannot be dissociated physically from the polymer­ ase activity.

Induction of biological activity by limited proteolysis.

Abstract: important papers in the present review. The splitting of large protein molecules by proteolytic enzymes is nec­ essarily a complicated process: the peptide chains may be split at a large number of potenti al sites determined by the specificity of the proteolytic enzyme and by the amino acid sequence of the peptide chains. Even in the cases where the peptide chains are in unfolded forms, all of these potential sites need not be split, since different peptide bonds are attacked at dif­ ferent rates and the opening of one bond might influence the rate of split­ ting of an adjacent bond. The situation is even more complicated in the globular proteins where the peptide chain is folded into a compact three-di­ mensional structure which prevents some or all of the peptide bonds from having the correct contact with the active site of the enzyme. In these cases the pep tide chains will only be split at those bonds where the sur­ rounding segment of the peptide chain meets the specificity require­ ments of the enzyme and has sufficient flexibilit y to fit into its active site. Depending upon the stability of the protein structure, the further prote­