Abstract

Inhibitory effect of agents altering the structure of DNA on the synthesis of pyrimidine deoxyribonucleotides in bacteriophage T4 DNA replication.

Highlights

  • Mitomycin C, an agent causing interstrand cross-linking between guanine residues, was administered to cultures infected by a phage T4x- strain after early protein synthesis was completed

  • Since the product of gene x repairs DNA damage caused by mitomycin C, these findings provide strong argument that the action of this agent is through its reaction with DNA and not by direct inactivation of enzymes in the synthetic pathway to deoxyribonucleotides

  • The results of this study clearly show that agents which modify the structure of the DNA template by a variety of mechanisms inhibit phage T4 DNA replication and the de novo synthesis of the pyrimidine deoxyribonucleotides

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Summary

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Inhibitory Effect of Agents Altering the Structure of DNA on the Synthesis of Pyrimidine Deoxyribonucleotides in Bacteriophage T4 DNA Replication*. Because of our earlier studies suggesting a direct role of the deoxyribonucleotide-synthesizing enzymes in DNA replication (6-81, comparable experiments from other laboratories (g-11), and new evidence of a channeled synthesis of deoxyribonucleotides (121, we have proposed that the regulation is intrinsic in the structure and activity of a complex of enzymes (1). If so, altering its structure might affect DNA synthesis but the in uiuo activities of the enzymes forming deoxyribonucleotides To test such a possibility, we have used various agents known to alter DNA, using the in uivo assay described. The present study shows that such agents do, have a profound effect on the regulation of deoxyribonucleotide biosynthesis, apparently without affecting the in vitro activities or the induction of the phage-induced early enzymes

PROCEDURES
Agents on Release
COYTROI i
Con Deoxyribonucleotide
TABLE I
Findings
DISCUSSION
Full Text
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