Transcription by eucaryotic and procaryotic RNA polymerases of DNA modified at a d(GG) or a d(AG) site by the antitumor drug cis-diamminedichloroplatinum (II)

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00215a032· OSTI ID:5527240

Corda, Y; Job, C; Job, D ^[1]; Anin, M-F; Leng, M ^[2]

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1. Centre de Biochimie et de Biologie Moleculaire, Marseille (France)
2. Centre de Biophysique Moleculaire, Orleans (France)

The authors have investigated whether DNA modifed at a d(GG) or a d(AG) site by the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-DDP) can be used as template by wheat germ RNA polymerase II. The templates used in the present study were obtained by ligation of double-helical oligodeoxyribonucleotides, containing 18 pyrimidine bases and 2 central dG, or dA and dG, bases on one strand and 18 purine bases and 2 central dC, or dT and dC, bases on the complementary strand. Therefore, the cis-DDP adducts are only present on one strand of each of the two templates and are regularly spaced by 18 pyrimidine bases. These constructs allowed the authors to investigate the effect of cis-DDP on transcription of the platinated strand and of the complementary unplatinated sequence. Transcription experiments were carried out in the presence of dinucleotide primers and either a single triphosphate substrate (abortive elongation) or the full set of triphosphate substrates dictated by the template sequence (productive elongation). The results show taht the eucraryotic RNA polymerase can catalyze dinucleotide-primed reactions on platinated DNA. However, the eurcaryotic enzyme behaved very differently depending on which strand was transcribed. Thus, transcription elongation was completely blocked on the strand carrying the metal complex, whereas transcription elongation was not blocked on the complementary template strand. Similar results were obtained in transcription of the platinated templates by Escherichia coli RNA polymerase, suggesting that the cis-DDP-induced effect is associated with modifications of the basic catalytic properties of the transcriptases.

• OSTI ID: 5527240
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 30:1; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
DAYS LIVING RADIOISOTOPES
ENZYMES
ESCHERICHIA COLI
ISOTOPES
LIGHT NUCLEI
MICROORGANISMS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PLATINUM COMPOUNDS
POLYMERASES
RADIOISOTOPES
RNA POLYMERASES
TRANSCRIPTION
TRANSFERASES
TRANSITION ELEMENT COMPOUNDS