Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study

[Image: see text] Errors in epigenetic markings are associated with human diseases, including cancer. We have used molecular dynamics simulations of a nucleosome containing the 10S (+)-trans-anti-B[a]P-N(2)-dG lesion, derived from the environmental pro-carcinogen benzo[a]pyrene, to elucidate the impact of the lesion on the structure and dynamics of a nearby histone N-terminal tail. Our results show that a lysine-containing part of this H2B tail that is subject to post-translational modification is engulfed by the enlarged DNA minor groove imposed by the lesion. The tail entrapment suggests that epigenetic markings could be hampered by this lesion, thereby impacting critical cellular functions, including transcription and repair.