Work

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

Year: 1997

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.94.25.13448

Authors: Julia Yaneva, Sanford H. Leuba, Kensal van Holde, Jordanka Zlatanova

Institutions: Oregon State University, Bulgarian Academy of Sciences, Institute of Molecular Biology

Language: English

Topic: Metal complexes synthesis and properties

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, Fogarty International Center

Awards: G1681749087, H-1 HYPERSITES, G4386317277, LINKER HISTONE/DNA INTERACTIONS