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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 imp...

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Autores principales: Fu, Iwen, Cai, Yuqin, Zhang, Yingkai, Geacintov, Nicholas E., Broyde, Suse
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721520/
https://www.ncbi.nlm.nih.gov/pubmed/26709619
http://dx.doi.org/10.1021/acs.biochem.5b01166
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author Fu, Iwen
Cai, Yuqin
Zhang, Yingkai
Geacintov, Nicholas E.
Broyde, Suse
author_facet Fu, Iwen
Cai, Yuqin
Zhang, Yingkai
Geacintov, Nicholas E.
Broyde, Suse
author_sort Fu, Iwen
collection PubMed
description [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.
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spelling pubmed-47215202016-12-28 Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study Fu, Iwen Cai, Yuqin Zhang, Yingkai Geacintov, Nicholas E. Broyde, Suse Biochemistry [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. American Chemical Society 2015-12-28 2016-01-19 /pmc/articles/PMC4721520/ /pubmed/26709619 http://dx.doi.org/10.1021/acs.biochem.5b01166 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Fu, Iwen
Cai, Yuqin
Zhang, Yingkai
Geacintov, Nicholas E.
Broyde, Suse
Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
title Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
title_full Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
title_fullStr Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
title_full_unstemmed Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
title_short Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
title_sort entrapment of a histone tail by a dna lesion in a nucleosome suggests the lesion impacts epigenetic marking: a molecular dynamics study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721520/
https://www.ncbi.nlm.nih.gov/pubmed/26709619
http://dx.doi.org/10.1021/acs.biochem.5b01166
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