Effect of nucleosome structure on DNA interstrand cross-linking reactions

Biochemistry
J T MillardP B Hopkins

Abstract

Antitumor agents of the nitrogen mustard family and mitomycin C form interstrand cross-links in duplex DNA. To provide information about the cellular mechanism by which these compounds exert their cytotoxic effects, we examined cross-linking of a nucleosomal core particle formed on a fragment of the 5S RNA gene of Xenopus borealis. For the mustards mechlorethamine, chlorambucil, and melphalan, both sites of monoalkylation and interstrand cross-linking were similar in nucleosomal and free DNA. Some small (two- to three- fold) differences in intensity of cross-linking at some sites were apparent. However, these differences did not appear to correlate with rotational or translational positioning. For mitomycin C, cross-linking was inhibited five- to ten-fold at the nucleosomal dyad and showed attenuation of inhibition toward the ends. Furthermore, rotational positioning also appeared to be a factor, with sites facing inward in the nucleosome less accessible for mitomycin cross-linking. None of these agents demonstrated the 10-base pair periodicity exhibited by hydroxyl radical cleavage of nucleosomal DNA.

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Citations

Mar 17, 2004·Biosensors & Bioelectronics·Robert J Mitchell, Man Bock Gu
Jan 18, 2006·Chemical Research in Toxicology·Julie T MillardNatalia Tretyakova
Dec 23, 2009·Nucleic Acids Research·Gabriela E DaveyCurt A Davey
Jan 20, 2006·Nature Chemical Biology·Kent S Gates
Oct 18, 2008·Chemical Biology & Drug Design·Gabriela E Davey, Curt A Davey
Jun 23, 2010·Chemical Biology & Drug Design·Anne M Galea, Vincent Murray
Aug 4, 2005·Biosensors & Bioelectronics·Jin Hyung LeeMan Bock Gu
Feb 1, 2005·Biosensors & Bioelectronics·Jin Hyung Lee, Man Bock Gu
Sep 11, 2004·Biochimie·J T MillardD M Thamattoor
May 26, 2007·Chemistry & Biology·Vidya SubramanianKarolin Luger
Nov 6, 2020·Chemical Research in Toxicology·Shane R Byrne, Steven E Rokita
Nov 16, 2019·Chemical Research in Toxicology·Mengdi ShangChuanzheng Zhou
Mar 19, 2019·Chemical Research in Toxicology·Shane R ByrneSteven E Rokita

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