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Published on: November 10, 2016
Interaction of histone H1 with cis-platinum modified DNA
E G Paneva1, N C Spassovska, K C Grancharov
1Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Abstract:
Cis-diamminedichloroplatinum(II) (cis-DDP) is known as an effective anticancer drug. Its therapeutic effect is supposed to be a consequence of the covalent binding to DNA. A number of cellular proteins were found to bind selectively to DNA modified by cis-DDP (but not by its isomer trans-DDP). Here we present our observations on interaction of the linker histone H1 with cis- and trans-DDP modified DNA fragments. The results afford new experimental information about the preferential binding of histone H1 to cis-DDP-distorted DNAs versus trans-DDP modified ones.
Insights
The anticancer drug cisplatin (cis-DDP) binds to DNA, and histone H1 protein preferentially interacts with DNA damaged by cis-DDP compared to its isomer trans-DDP.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- Cis-diamminedichloroplatinum(II) (cis-DDP) is a platinum-based chemotherapy agent with established efficacy against various cancers.
- The therapeutic action of cis-DDP is primarily attributed to its covalent interaction with cellular DNA, leading to DNA damage and apoptosis.
- Specific cellular proteins exhibit selective binding to DNA modified by cis-DDP, distinguishing it from its isomer, trans-DDP.
Purpose of the Study:
- To investigate the interaction between the linker histone H1 and DNA fragments modified by cis-diamminedichloroplatinum(II) (cis-DDP) and its isomer trans-DDP.
- To provide experimental evidence regarding the preferential binding of histone H1 to cis-DDP-modified DNA structures.
Main Methods:
- Preparation of DNA fragments modified with cis-DDP and trans-DDP.
- Experimental analysis of the binding affinity and specificity of linker histone H1 to these modified DNA fragments.
Main Results:
- Histone H1 demonstrated preferential binding to DNA fragments modified by cis-DDP.
- The binding of histone H1 to trans-DDP modified DNA fragments was significantly less pronounced compared to cis-DDP modified DNA.
- These findings highlight the distinct conformational changes induced in DNA by cis- and trans-DDP and their differential recognition by histone H1.
Conclusions:
- Linker histone H1 exhibits a preference for binding to DNA that has been distorted by cis-diamminedichloroplatinum(II) (cis-DDP) adducts.
- This preferential interaction suggests a role for histone H1 in recognizing and potentially responding to cis-DDP-induced DNA damage.
- The differential binding provides new insights into the molecular mechanisms underlying cis-DDP's anticancer activity and cellular responses to platinum-based chemotherapy.
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