A Dynamic View of the Interaction of Histone Tails with Clustered Abasic Sites in a Nucleosome Core Particle

Apurinic/apyrimidinic sites are the most common forms of DNA damage under physiological conditions, yet their structural and dynamical behavior within nucleosome core particles has just begun to be investigated is dramatically different from that abasic in B-DNA. Clusters two or more repaired even less efficiently hence constitute hot spots high mutagenicity notably due enhanced double-strand break formation. On basis an X-ray structure a 146 bp wrapped onto histone core, we investigate bistranded positioned at mutational during microsecond-range molecular dynamics simulations. Our simulations allow us probe interactions tails clustered site locations, with definitive assignment key residues involved NCP-catalyzed formation DNA-protein cross-linking line recent experimental findings, pave way for systematic assessment response lesions.