Structural and Thermodynamic Impact of Oncogenic Mutations on the Nucleosome Core Particle.

ABSTRACT: The nucleosome core particle (NCP) is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. Here, we investigate the molecular consequences of two mutations-H2BE76K and H4R92T-using 36 μs of all-atom molecular dynamics simulations and experimental biophysical assays. These mutations destabilize the H2B-H4 interface by disrupting critical salt bridges and hydrogen bonds, reducing binding free energy at this interface. Principal component analysis reveals altered helix conformations and increased interhelical distances in mutant systems. Thermal stability assays (TSA) and differential scanning calorimetry (DSC) confirm that these

SUBMITTER: Onyema AC 

PROVIDER: S-EPMC11844553 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature