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Cisplatin fastens chromatin irreversibly even at a high chloride concentration

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Title
Cisplatin fastens chromatin irreversibly even at a high chloride concentration
Author(s)
Hyeon-Min Moon; Jin-Sung Park; Il-Buem Lee; Kang, Young-Im; Jung, Hae Jun; An, Dongju; Shin, Yumi; Kim, Min Ji; Kim, Hugh, I; Song, Ji-Joon; Kim, Jaehoon; Lee, Nam-Kyung; Seok-Cheol Hong
Publication Date
2021-12-02
Journal
NUCLEIC ACIDS RESEARCH, v.49, no.21, pp.12035 - 12047
Publisher
OXFORD UNIV PRESS
Abstract
Cisplatin is one of the most potent anti-cancer drugs developed so far. Recent studies highlighted several intriguing roles of histones in cisplatin's anti-cancer effect. Thus, the effect of nucleosome formation should be considered to give a better account of the anti-cancer effect of cisplatin. Here we investigated this important issue via single-molecule measurements. Surprisingly, the reduced activity of cisplatin under [NaCl] = 180 mM, corresponding to the total concentration of cellular ionic species, is still sufficient to impair the integrity of a nucleosome by retaining its condensed structure firmly, even against severe mechanical and chemical disturbances. Our finding suggests that such cisplatin-induced fastening of chromatin can inhibit nucleosome remodelling required for normal biological functions. The in vitro chromatin transcription assay indeed revealed that the transcription activity was effectively suppressed in the presence of cisplatin. Our direct physical measurements on cisplatin-nucleosome adducts suggest that the formation of such adducts be the key to the anti-cancer effect by cisplatin.
URI
https://pr.ibs.re.kr/handle/8788114/10986
DOI
10.1093/nar/gkab922
ISSN
0305-1048
Appears in Collections:
Center for Molecular Spectroscopy and Dynamics(분자 분광학 및 동력학 연구단) > 1. Journal Papers (저널논문)
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