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PMID: 9391045 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The major chromatin protein histone H1 binds preferentially to cis-platinum-damaged DNA.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 25 ·1997-12-09 ·Pages 13448-51

Yaneva J, Leuba SH, van Holde K, Zlatanova J

Abstract

Both cis-diamminedichloroplatinum(II) (cisplatin or cis-DDP) and trans-diamminedichloroplatinum(II) form covalent adducts with DNA. However, only the cis isomer is a potent anticancer agent. It has been postulated that the selective action of cis-DDP occurs through specific binding of nuclear proteins to cis-DDP-damaged DNA sites and that binding blocks DNA repair. We find that a very abundant nuclear protein, the linker histone H1, binds much more strongly to cis-platinated DNA than to trans-platinated or unmodified DNA. In competition experiments, H1 is shown to bind much more strongly than HMG1, which had been previously considered a major candidate for such binding in vivo.

MeSH Terms
Animals Antineoplastic Agents/metabolism,pharmacology Base Sequence Binding Sites Binding, Competitive Cisplatin/metabolism,pharmacology DNA/drug effects,genetics,metabolism DNA Adducts/genetics,metabolism DNA Damage DNA Repair/drug effects High Mobility Group Proteins/metabolism Histones/metabolism In Vitro Techniques Kinetics Mice
Chemicals
Antineoplastic Agents DNA Adducts High Mobility Group Proteins Histones DNA Cisplatin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yaneva J
Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Leuba S H
van Holde K
Zlatanova J
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34 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.25.13448
Published
1997-12-09
Pages
13448-51
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC28325
Subset
IM
Grants
NIGMS NIH HHS · GM50276 · United States
FIC NIH HHS · TW00568-02 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.25.13448 PMC Full Text View journal details
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