Novobiocin precipitates histones at concentrations normally used to inhibit eukaryotic type II topoisomerase

Cotten, M. , Bresnahan, D., Thompson, S., Sealy, L. and Chalkeley, R. (1986) Novobiocin precipitates histones at concentrations normally used to inhibit eukaryotic type II topoisomerase. Nucleic Acids Research, 14(9), pp. 3671-3686. (doi: 10.1093/nar/14.9.3671) (PMID:3714493) (PMCID:PMC339807)

Abstract

At concentrations normally used to inhibit eukaryotic type II topoisomerase activity (100–1000 μg/ml) novobiocin binds core histones. Approximately 15 moles of novobiocin bind per mole of histone resulting in histone precipitation from solution in either 0.15 M or 2 M NaCl. The interaction between novobiocin and proteins appears to involve arginine residues: histones H3 and H4 (13.5 and 14 mole percent arginine) are precipitated at lower novobiocin concentrations than histones H2A and H2B (9.5 and 6.5 mole percent arginine). Furthermore, polyarginine but not polyornithine competes for novobiocin in histone precipitation. Moreover, histones with arginine residues modified with 1,2-cyclohexanedione are soluble in 1000 μg/ml novobiocin. Because novobiocin can remove histones from solution as well as inhibit topoisomerase activity, and because both of these events can alter DNA topology, novobiocin should be used with caution in experiments designed to implicate topoisomerase activity in chromatin dynamics.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cotten, Professor Matthew
• Authors: Cotten, M., Bresnahan, D., Thompson, S., Sealy, L., and Chalkeley, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Nucleic Acids Research
• Publisher: IRL Press
• ISSN: 0305-1048
• ISSN (Online): 1362-4962