PMID: 6402759Feb 25, 1983Paper

Specific inhibitors of eukaryotic DNA synthesis and DNA polymerase alpha, 3-deoxyaphidicolin and aphidicolin-17-monoacetate

Nucleic Acids Research
T HaraguchiS Sakamura

Abstract

Of several phytotoxins isolated from culture filtrates of Phoma betae Frank PS-13, an incitant of leaf spot disease of sugar beet, three have been identified as aphidicolin, 3-deoxyaphidicolin and aphidicolin-17-monoacetate. Aphidicolin is a selective inhibitor of eukaryotic DNA polymerase alpha (Ikegami et al. (1978) Nature 275, 458-460). Consequently, we studied the action mechanism of 3-deoxyaphidicolin and aphidicolin-17-monoacetate. These aphidicolin analogues markedly inhibited the in vivo DNA synthesis of sea urchin embryos and HeLa cells but not RNA and protein syntheses. Only DNA polymerase alpha, not DNA polymerase beta and gamma, was inhibited by these drugs. The mode of action of these analogues on DNA polymerase alpha from the sea urchin was competitive inhibition with respect to dCTP with Ki values of 0.44 micrograms/ml for deoxyaphidicolin and 0.89 micrograms/ml for aphidicolin monoacetate, respectively. None of the other three dNTPs competed with these drugs. A similar inhibitory mode was observed using the enzyme from HeLa cells and toad oocytes. These drugs at a concentration of 2 micrograms/ml caused a delay in the cleavage of fertilized eggs of the sea urchin and decomposition before blastulation, indicating...Continue Reading

References

Jul 1, 1979·European Journal of Biochemistry·M OguroS Ikegami
Sep 1, 1973·Antimicrobial Agents and Chemotherapy·R A BucknallB Hesp
Jul 30, 1981·Developmental Biology·H NaganoS Ikegami
Jun 15, 1982·Biochemical and Biophysical Research Communications·H NaganoC Katagiri
Jan 15, 1980·Biochemical and Biophysical Research Communications·M OguroM Yamada
Jan 15, 1980·Biochemical and Biophysical Research Communications·A HabaraT Yamashita

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Citations

Jan 1, 1990·Pharmacology & Therapeutics·G E Wright, N C Brown
Apr 1, 1985·Antiviral Research·S SpadariG Pedrali-Noy
May 1, 1987·The Journal of Cell Biology·D E Olins, A L Olins
Jun 10, 1988·Nucleic Acids Research·L ArabshahiG Wright
Mar 11, 2006·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Akira KuroseZbigniew Darzynkiewicz
Nov 29, 2014·Nucleic Acids Research·Andrey G BaranovskiyTahir H Tahirov
Jun 24, 2009·Chemical Reviews·Mats Ljungman

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