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Updated: Aug 15, 2026
16:24
Analyzing and Building Nucleic Acid Structures with 3DNA
Published on: April 26, 2013
New insights into calicheamicin-DNA interactions derived from a model nucleosome system
L Yu1, A A Salzberg, P C Dedon
1Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Bioorganic & Medicinal Chemistry
|June 1, 1995
Summary
Calicheamicin (CAL) antitumor drug interactions with DNA were studied. Nucleosomes generally reduced CAL DNA damage, but sometimes enhanced it, revealing new drug-DNA interaction insights.
Area of Science:
- Molecular Biology
- Drug Discovery
- Genetics
Background:
- Calicheamicin (CAL) is an enediyne antitumor agent.
- Understanding drug-DNA interactions is crucial for cancer therapy.
- Nucleosomes package DNA, potentially altering drug binding.
Purpose of the Study:
- Investigate CAL interactions with nucleosomal and naked DNA targets.
- Determine CAL target selection mechanisms.
- Explore how DNA incorporation into nucleosomes affects CAL-induced damage.
Main Methods:
- Utilized the Xenopus borealis 5S RNA gene as a model.
- Compared CAL-mediated DNA damage in nucleosomal vs. naked DNA.
- Determined the orientation of CAL at damage sites in naked DNA.
Main Results:
- Nucleosomal DNA generally showed reduced CAL damage compared to naked DNA.
- Specific nucleosomal sites exhibited enhanced CAL damage.
- CAL target selection depends on interrupted oligopurine tracts, not solely minor groove width.
- The dyad axis of the 5S rRNA gene nucleosome could not be precisely determined.
Conclusions:
- DNA incorporation into chromatin creates unique structural features influencing drug interactions.
- CAL recognizes specific structural and dynamic features at the 3'-end of interrupted oligopurine tracts.
- Limitations in nucleosome structure determination impact drug-DNA interaction studies.
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01:16The DNA Helix
Overview
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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
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Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
02:21Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
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The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
01:32Chromatin Packaging
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...