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

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Abstract

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-N2-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.

Original languageEnglish (US)
Pages (from-to)239-242
Number of pages4
JournalBiochemistry
Volume55
Issue number2
DOIs
StatePublished - Jan 19 2016

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Nucleosomes
Benzo(a)pyrene
Molecular Dynamics Simulation
Transcription
Epigenomics
Carcinogens
Histones
Lysine
Molecular dynamics
Tail
Repair
DNA
Computer simulation
Environmental Carcinogens
Post Translational Protein Processing
benzo(a)pyrene N2-dG adduct
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study",
abstract = "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-N2-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.",
author = "Iwen Fu and Yuqin Cai and Yingkai Zhang and Geacintov, {Nicholas E.} and Suse Broyde",
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T1 - Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking

T2 - A Molecular Dynamics Study

AU - Fu, Iwen

AU - Cai, Yuqin

AU - Zhang, Yingkai

AU - Geacintov, Nicholas E.

AU - Broyde, Suse

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AB - 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-N2-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.

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