PMID: 9427537Jan 14, 1998Paper

High-mobility group 1 protein inhibits helicase catalyzed displacement of cisplatin-damaged DNA

Biochimica Et Biophysica Acta
S M PatrickJ J Turchi

Abstract

We have determined the effect of HMG-1 bound to cisplatin-damaged DNA on the activities of calf helicase E. DNase I protection analysis demonstrated HMG-1 bound a cisplatin-damaged 24 base oligonucleotide annealed to M13mp18. Exonuclease digestion experiments revealed that greater than 90% of the DNA substrates contained a single site specific cisplatin adduct and, maximally, 65% of the substrates were bound by HMG-1. Helicase E catalyzed displacement of the cisplatin-damaged DNA oligonucleotide was inhibited by HMG-1 in a concentration-dependent manner. Time course experiments revealed a decreased rate of displacement in reactions containing HMG-1. The maximum inhibition observed was 55% and taking into account that only 65% of the substrates had HMG-1 bound, approximately 85% inhibition was observed on platinated DNA substrates containing HMG-1. Inhibition of helicase activity was proportional to the amount of substrate bound by HMG-1 based on the displacement and exonuclease assays at varying HMG-1 concentrations. The ability of helicase E to displace an undamaged DNA oligonucleotide from a cisplatin-damaged DNA template was also inhibited by HMG-1. Interestingly, HMG-1 had no effect on the rate of DNA-dependent ATP hydrolys...Continue Reading

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Citations

Jul 11, 2014·Molecular Aspects of Medicine·Rui KangDaolin Tang
Jun 2, 2000·Protein Expression and Purification·I L Hermanson, J J Turchi
Aug 24, 2000·The Journal of Biological Chemistry·G Villani, N Tanguy Le Gac
May 23, 2000·Teratogenesis, Carcinogenesis, and Mutagenesis·J BlasiakM Wojewódzka
Jan 18, 2005·The Journal of Biological Chemistry·John M CasperMichael Leffak
Jan 8, 2020·International Journal of Molecular Sciences·Yukiko NishiguchiHiroki Kuniyasu

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