Monitoring Anthracycline Cancer Drug-Nucleosome Interaction by NMR using a Specific Isotope Labeling Approach for Nucleosomal DNA

We describe the synthesis of segmental one-strand 13C-thymidine labeled 601-DNA, the assignment of the methyl signals, and demonstrate its use to observe site-specific binding events in the nucleosome by aclarubicin, an anthracycline cancer drug that intercalates into the DNA minor grooves. Our results highlight intrinsic conformational heterogeneity in the 601 DNA sequence and show that aclarubicin binds an exposed AT-rich region near the DNA end. Overall, our data point to a model where the drug invades the nucleosome from the terminal ends inward, eventually resulting in histone eviction and nucleosome disruption.PMID:38476018 | DOI:10.1002/cbic.202400111

Source: Chembiochem - March 13, 2024 Category: Biochemistry Authors: Clara L van Emmerik Vincenzo Lobbia Jacques Neefjes Frank H T Nelissen Hugo van Ingen Source Type: research