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Effects of coordination of diammineplatinum(II) with DNA on the activities of Escherichia coli DNA polymerase I

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00417a031· OSTI ID:6464692
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The effects of the reaction of cis- and trans-diamminedichloroplatinum(II) with DNA have been measured with regard to DNA synthesis, 3'-5' exonuclease (proofreading), and 5'-3' exonuclease (repair) activities of Escherichia coli DNA polymerase I. Both isomers inhibit DNA synthetic activity of the polymerase through an increase in K/sub m/ values and a decrease in V/sub max/ values for platinated DNA but not for the nucleoside 5'-triphosphates as the varied substrates. The inhibition is a consequence of lowered binding affinity between platinated DNA and DNA polymerase, and of a platination-induced separation of template and primer strands. Strand separation enhances initial rates of 3'-5' excision of (/sup 3/H)dCMP from platinated DNA (proofreading), while total excision levels of nucleotides are decreased. In contrast to proofreading activity, the 5'-3' exonuclease activity (repair) discriminates between DNA which had reacted with cis- and with trans-diamminedichloroplatinum(II). While both initial rates and total excision are inhibited for the cis isomer, they are almost not affected for the trans isomer. This differential effect could explain why bacterial growth inhibition requires much higher concentrations of trans- than cis-diamminedichloroplatinum(II).

Research Organization:
Universitaetsstrasse, Regensburg (Germany, F.R.)
OSTI ID:
6464692
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:17; ISSN BICHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DAYS LIVING RADIOISOTOPES
DNA POLYMERASES
DNA REPAIR
DNA REPLICATION
ENZYMES
ESCHERICHIA COLI
INHIBITION
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
MICROORGANISMS
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOTIDYLTRANSFERASES
ODD-ODD NUCLEI
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PLATINUM COMPOUNDS
POLYMERASES
RADIOISOTOPES
REACTION KINETICS
RECOVERY
REPAIR
STEREOCHEMISTRY
TRANSFERASES
TRANSITION ELEMENT COMPOUNDS
TRITIUM COMPOUNDS