Synergistic effects of H3 and H4 nucleosome tails on structure and dynamics of a lesion-containing DNA: Binding of a displaced lesion partner base to the H3 tail for GG-NER recognition
Abstract
How DNA lesions in nucleosomes are recognized for global genome nucleotide excision repair (GG-NER) remains poorly understood, and the roles that histone tails may play remains to be established. Histone H3 and H4 N-terminal tails are of particular interest as their acetylation states are important in regulating nucleosomal functions in transcription, replication and repair. In particular the H3 tail has been the focus of recent attention as a site for the interaction with XPC, the GG-NER lesion recognition factor. Here we have investigated how the structure and dynamics of the DNA lesion cis-B[a]P-dG, derived from the environmental carcinogen benzo[a]pyrene (B[a]P), is impacted by the presence of flanking H3 and H4 tails. This lesion is well-repaired by GG-NER, and adopts a base-displaced/intercalated conformation in which the lesion partner C is displaced into the major groove. We used molecular dynamics simulations to obtain structural and dynamic characterizations for this lesion positioned in nucleosomal DNA so that it is bracketed by the H3 and H4 tails. The H4 tail was studied in unacetylated and acetylated states, while the H3 tail was unacetylated, its state when it binds XPC (Kakumu, Nakanishi et al., 2017). Our results reveal that upon acetylation, the H4 tail ismore »
- Authors:
-
- New York Univ. (NYU), NY (United States)
- New York Univ. (NYU), NY (United States); NYU-ECNU Center for Computational Chemistry, Shanghai (China)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1543539
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- DNA Repair
- Additional Journal Information:
- Journal Volume: 65; Journal Issue: C; Journal ID: ISSN 1568-7864
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Genetics & Heredity; Toxicology
Citation Formats
Cai, Yuqin, Fu, Iwen, Geacintov, Nicholas E., Zhang, Yingkai, and Broyde, Suse. Synergistic effects of H3 and H4 nucleosome tails on structure and dynamics of a lesion-containing DNA: Binding of a displaced lesion partner base to the H3 tail for GG-NER recognition. United States: N. p., 2018.
Web. doi:10.1016/j.dnarep.2018.02.009.
Cai, Yuqin, Fu, Iwen, Geacintov, Nicholas E., Zhang, Yingkai, & Broyde, Suse. Synergistic effects of H3 and H4 nucleosome tails on structure and dynamics of a lesion-containing DNA: Binding of a displaced lesion partner base to the H3 tail for GG-NER recognition. United States. https://doi.org/10.1016/j.dnarep.2018.02.009
Cai, Yuqin, Fu, Iwen, Geacintov, Nicholas E., Zhang, Yingkai, and Broyde, Suse. Thu .
"Synergistic effects of H3 and H4 nucleosome tails on structure and dynamics of a lesion-containing DNA: Binding of a displaced lesion partner base to the H3 tail for GG-NER recognition". United States. https://doi.org/10.1016/j.dnarep.2018.02.009. https://www.osti.gov/servlets/purl/1543539.
@article{osti_1543539,
title = {Synergistic effects of H3 and H4 nucleosome tails on structure and dynamics of a lesion-containing DNA: Binding of a displaced lesion partner base to the H3 tail for GG-NER recognition},
author = {Cai, Yuqin and Fu, Iwen and Geacintov, Nicholas E. and Zhang, Yingkai and Broyde, Suse},
abstractNote = {How DNA lesions in nucleosomes are recognized for global genome nucleotide excision repair (GG-NER) remains poorly understood, and the roles that histone tails may play remains to be established. Histone H3 and H4 N-terminal tails are of particular interest as their acetylation states are important in regulating nucleosomal functions in transcription, replication and repair. In particular the H3 tail has been the focus of recent attention as a site for the interaction with XPC, the GG-NER lesion recognition factor. Here we have investigated how the structure and dynamics of the DNA lesion cis-B[a]P-dG, derived from the environmental carcinogen benzo[a]pyrene (B[a]P), is impacted by the presence of flanking H3 and H4 tails. This lesion is well-repaired by GG-NER, and adopts a base-displaced/intercalated conformation in which the lesion partner C is displaced into the major groove. We used molecular dynamics simulations to obtain structural and dynamic characterizations for this lesion positioned in nucleosomal DNA so that it is bracketed by the H3 and H4 tails. The H4 tail was studied in unacetylated and acetylated states, while the H3 tail was unacetylated, its state when it binds XPC (Kakumu, Nakanishi et al., 2017). Our results reveal that upon acetylation, the H4 tail is released from the DNA surface; the H3 tail then forms a pocket that induces flipping and capture of the displaced lesion partner base C. This reveals synergistic effects of the behavior of the two tails. We hypothesize that the dual capability of the H3 tail to sense the displaced lesion partner base and to bind XPC could foster recognition of this lesion by XPC for initiation of GG-NER in nucleosomes.},
doi = {10.1016/j.dnarep.2018.02.009},
journal = {DNA Repair},
number = C,
volume = 65,
place = {United States},
year = {Thu Mar 08 00:00:00 EST 2018},
month = {Thu Mar 08 00:00:00 EST 2018}
}
Web of Science
Works referenced in this record:
New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?
journal, June 2012
- Luger, Karolin; Dechassa, Mekonnen L.; Tremethick, David J.
- Nature Reviews Molecular Cell Biology, Vol. 13, Issue 7
Nucleosome Structure and Function
journal, October 2014
- McGinty, Robert K.; Tan, Song
- Chemical Reviews, Vol. 115, Issue 6
Intra- and inter-nucleosome interactions of the core histone tail domains in higher-order chromatin structure
journal, August 2013
- Pepenella, Sharon; Murphy, Kevin J.; Hayes, Jeffrey J.
- Chromosoma, Vol. 123, Issue 1-2
Post-Translational Modifications of Histones That Influence Nucleosome Dynamics
journal, October 2014
- Bowman, Gregory D.; Poirier, Michael G.
- Chemical Reviews, Vol. 115, Issue 6
Emerging roles for histone modifications in DNA excision repair
journal, October 2016
- Mao, Peng; Wyrick, John J.
- FEMS Yeast Research, Vol. 16, Issue 7
Genome-wide Map of Nucleosome Acetylation and Methylation in Yeast
journal, August 2005
- Pokholok, Dmitry K.; Harbison, Christopher T.; Levine, Stuart
- Cell, Vol. 122, Issue 4
The language of covalent histone modifications
journal, January 2000
- Strahl, Brian D.; Allis, C. David
- Nature, Vol. 403, Issue 6765
The growing landscape of lysine acetylation links metabolism and cell signalling
journal, July 2014
- Choudhary, Chunaram; Weinert, Brian T.; Nishida, Yuya
- Nature Reviews Molecular Cell Biology, Vol. 15, Issue 8
Role of Histone Acetylation in Cell Cycle Regulation
journal, November 2015
- Koprinarova, Miglena; Schnekenburger, Michael; Diederich, Marc
- Current Topics in Medicinal Chemistry, Vol. 16, Issue 7
50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond
journal, December 2014
- Verdin, Eric; Ott, Melanie
- Nature Reviews Molecular Cell Biology, Vol. 16, Issue 4
Sodium butyrate stimulates DNA repair in UV-irradiated normal and xeroderma pigmentosum human fibroblasts.
journal, November 1982
- Smerdon, M. J.; Lan, S. Y.; Calza, R. E.
- Journal of Biological Chemistry, Vol. 257, Issue 22
Changes in nuclear protein acetylation in u.v.-damaged human cells
journal, January 1986
- Ramanathan, Brinda; Smerdon, Michael J.
- Carcinogenesis, Vol. 7, Issue 7
Enhanced DNA Repair Synthesis in Hyperacetylated Nucleosomes
journal, July 1989
- Ramanathan, B.; Smerdon, M. J.
- Journal of Biological Chemistry, Vol. 264, Issue 19
Implication of Posttranslational Histone Modifications in Nucleotide Excision Repair
journal, September 2012
- Li, Shisheng
- International Journal of Molecular Sciences, Vol. 13, Issue 12
Chromatin dynamics after DNA damage: The legacy of the access–repair–restore model
journal, December 2015
- Polo, Sophie E.; Almouzni, Geneviève
- DNA Repair, Vol. 36
DNA repair and the role of chromatin structure
journal, June 1991
- Smerdon, Michael J.
- Current Opinion in Cell Biology, Vol. 3, Issue 3
Nucleosome rearrangement in human chromatin during UV-induced DNA- reapir synthesis.
journal, September 1978
- Smerdon, M. J.; Lieberman, M. W.
- Proceedings of the National Academy of Sciences, Vol. 75, Issue 9
Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays
journal, October 2016
- Mishra, Laxmi N.; Pepenella, Sharon; Rogge, Ryan
- Scientific Reports, Vol. 6, Issue 1
Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions
journal, February 2006
- Shogren-Knaak, M.
- Science, Vol. 311, Issue 5762
30 nm Chromatin Fibre Decompaction Requires both H4-K16 Acetylation and Linker Histone Eviction
journal, September 2008
- Robinson, Philip J. J.; An, Woojin; Routh, Andrew
- Journal of Molecular Biology, Vol. 381, Issue 4
Regulation of Nucleosome Stacking and Chromatin Compaction by the Histone H4 N-Terminal Tail–H2A Acidic Patch Interaction
journal, June 2017
- Chen, Qinming; Yang, Renliang; Korolev, Nikolay
- Journal of Molecular Biology, Vol. 429, Issue 13
Shaping chromatin for repair
journal, January 2013
- Gospodinov, Anastas; Herceg, Zdenko
- Mutation Research/Reviews in Mutation Research, Vol. 752, Issue 1
The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae
journal, April 2015
- Meas, Rithy; Smerdon, Michael J.; Wyrick, John J.
- Nucleic Acids Research, Vol. 43, Issue 10
Histones H3 and H4 require their relevant amino-tails for efficient nuclear import and replication-coupled chromatin assembly in vivo
journal, June 2017
- Ejlassi, Aïda; Menil-Philippot, Vanessa; Galvani, Angélique
- Scientific Reports, Vol. 7, Issue 1
Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure—a FRET study
journal, January 2015
- Gansen, Alexander; Tóth, Katalin; Schwarz, Nathalie
- Nucleic Acids Research, Vol. 43, Issue 3
Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3
journal, February 2017
- Kakumu, Erina; Nakanishi, Seiya; Shiratori, Hiromi M.
- Genes to Cells, Vol. 22, Issue 3
Nucleotide Excision Repair in Eukaryotes
journal, October 2013
- Scharer, O. D.
- Cold Spring Harbor Perspectives in Biology, Vol. 5, Issue 10
NMR Solution Structures of Stereoisomeric Covalent Polycyclic Aromatic Carcinogen−DNA Adducts: Principles, Patterns, and Diversity
journal, February 1997
- Geacintov, Nicholas E.; Cosman, Monique; Hingerty, Brian E.
- Chemical Research in Toxicology, Vol. 10, Issue 2
DNA Adduct Formation by Polycyclic Aromatic Hydrocarbon Dihydrodiol Epoxides
journal, January 1998
- Szeliga, Jan; Dipple, Anthony
- Chemical Research in Toxicology, Vol. 11, Issue 1
Base pair conformation-dependent excision of benzo[a]pyrene diol epoxide-guanine adducts by human nucleotide excision repair enzymes
journal, December 1997
- Hess, M. T.; Gunz, D.; Luneva, N.
- Molecular and Cellular Biology, Vol. 17, Issue 12
Resistance of bulky DNA lesions to nucleotide excision repair can result from extensive aromatic lesion–base stacking interactions
journal, July 2011
- Reeves, Dara A.; Mu, Hong; Kropachev, Konstantin
- Nucleic Acids Research, Vol. 39, Issue 20
The human DNA repair factor XPC-HR23B distinguishes stereoisomeric benzo[a]pyrenyl-DNA lesions
journal, May 2007
- Mocquet, Vincent; Kropachev, Konstantin; Kolbanovskiy, Marina
- The EMBO Journal, Vol. 26, Issue 12
Solution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex: Intercalation of the covalently attached benzo[a]pyrenyl ring into the helix and displacement of the modified deoxyguanosine
journal, April 1993
- Cosman, Monique; de los Santos, Carlos; Fiala, Radovan
- Biochemistry, Vol. 32, Issue 16
Nucleotide Excision Repair Lesion-Recognition Protein Rad4 Captures a Pre-Flipped Partner Base in a Benzo[ a ]pyrene-Derived DNA Lesion: How Structure Impacts the Binding Pathway
journal, May 2017
- Mu, Hong; Geacintov, Nicholas E.; Min, Jung-Hyun
- Chemical Research in Toxicology, Vol. 30, Issue 6
Recognition of DNA damage by the Rad4 nucleotide excision repair protein
journal, September 2007
- Min, Jung-Hyun; Pavletich, Nikola P.
- Nature, Vol. 449, Issue 7162
DNA Stretching and Extreme Kinking in the Nucleosome Core
journal, May 2007
- Ong, Michelle S.; Richmond, Timothy J.; Davey, Curt A.
- Journal of Molecular Biology, Vol. 368, Issue 4
Differences in the Access of Lesions to the Nucleotide Excision Repair Machinery in Nucleosomes
journal, June 2015
- Cai, Yuqin; Kropachev, Konstantin; Terzidis, Michael A.
- Biochemistry, Vol. 54, Issue 27
Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA.
journal, March 1992
- Cosman, M.; de los Santos, C.; Fiala, R.
- Proceedings of the National Academy of Sciences, Vol. 89, Issue 5
Entrapment of a Histone Tail by a DNA Lesion in a Nucleosome Suggests the Lesion Impacts Epigenetic Marking: A Molecular Dynamics Study
journal, January 2016
- Fu, Iwen; Cai, Yuqin; Zhang, Yingkai
- Biochemistry, Vol. 55, Issue 2
Nucleosome Histone Tail Conformation and Dynamics: Impacts of Lysine Acetylation and a Nearby Minor Groove Benzo[ a ]pyrene-Derived Lesion
journal, March 2017
- Fu, Iwen; Cai, Yuqin; Geacintov, Nicholas E.
- Biochemistry, Vol. 56, Issue 14
Histone H4 acetylation in human cells Frequency of acetylation at different sites defined by immunolabeling with site-specific antibodies
journal, August 1989
- Turner, Bryan M.; O'Neill, Laura P.; Allan, Irene M.
- FEBS Letters, Vol. 253, Issue 1-2
Patterns of histone acetylation
journal, November 1990
- Thorne, Alan W.; Kmiciek, Daniel; Mitchelson, Keith
- European Journal of Biochemistry, Vol. 193, Issue 3
Histone H4 acetylation in Drosophila Frequency of acetylation at different sites defined by immunolabelling with site-specific antibodies
journal, June 1991
- Munks, Rebecca J. L.; Moore, Jayne; O'Neill, Laura P.
- FEBS Letters, Vol. 284, Issue 2
Selective use of H4 acetylation sites in the yeast Saccharomyces cerevisiae
journal, September 1993
- Clarke, D. J.; O'Neill, L. P.; Turner, B. M.
- Biochemical Journal, Vol. 294, Issue 2
Non-random acetylation of histone H4 by a cytoplasmic histone acetyltransferase as determined by novel methodology
journal, July 1994
- Sobel, R. E.; Cook, R. G.; Allis, C. D.
- Journal of Biological Chemistry, Vol. 269, Issue 28
Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines
journal, September 1996
- Kuo, Min-Hao; Brownell, James E.; Sobel, Richard E.
- Nature, Vol. 383, Issue 6597
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB
journal, July 2015
- Maier, James A.; Martinez, Carmenza; Kasavajhala, Koushik
- Journal of Chemical Theory and Computation, Vol. 11, Issue 8
PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data
journal, June 2013
- Roe, Daniel R.; Cheatham, Thomas E.
- Journal of Chemical Theory and Computation, Vol. 9, Issue 7
Clustering Molecular Dynamics Trajectories: 1. Characterizing the Performance of Different Clustering Algorithms
journal, October 2007
- Shao, Jianyin; Tanner, Stephen W.; Thompson, Nephi
- Journal of Chemical Theory and Computation, Vol. 3, Issue 6
VMD: Visual molecular dynamics
journal, February 1996
- Humphrey, William; Dalke, Andrew; Schulten, Klaus
- Journal of Molecular Graphics, Vol. 14, Issue 1
Aromatic–Proline Interactions: Electronically Tunable CH/π Interactions
journal, June 2012
- Zondlo, Neal J.
- Accounts of Chemical Research, Vol. 46, Issue 4
ASH1L histone methyltransferase regulates the handoff between damage recognition factors in global-genome nucleotide excision repair
journal, November 2017
- Balbo Pogliano, Chiara; Gatti, Marco; Rüthemann, Peter
- Nature Communications, Vol. 8, Issue 1
DNA Quality Control by Conformational Readout on the Undamaged Strand of the Double Helix
journal, August 2005
- Buterin, Tonko; Meyer, Christoph; Giese, Bernd
- Chemistry & Biology, Vol. 12, Issue 8
Base-Displaced Intercalated Structure of the Food Mutagen 2-Amino-3-methylimidazo[4,5- f ]quinoline in the Recognition Sequence of the Nar I Restriction Enzyme, a Hotspot for −2 bp Deletions
journal, August 2006
- Wang, Feng; DeMuro, Nicholas E.; Elmquist, C. Eric
- Journal of the American Chemical Society, Vol. 128, Issue 31
Repair-Resistant DNA Lesions
journal, July 2017
- Geacintov, Nicholas E.; Broyde, Suse
- Chemical Research in Toxicology, Vol. 30, Issue 8
Single-Molecule Imaging Reveals that Rad4 Employs a Dynamic DNA Damage Recognition Process
journal, October 2016
- Kong, Muwen; Liu, Lili; Chen, Xuejing
- Molecular Cell, Vol. 64, Issue 2
Real-Time Tracking of Parental Histones Reveals Their Contribution to Chromatin Integrity Following DNA Damage
journal, October 2016
- Adam, Salomé; Dabin, Juliette; Chevallier, Odile
- Molecular Cell, Vol. 64, Issue 1
Roll: a new algorithm for the detection of protein pockets and cavities with a rolling probe sphere
journal, October 2009
- Yu, Jian; Zhou, Yong; Tanaka, Isao
- Bioinformatics, Vol. 26, Issue 1
CASTp: Computed Atlas of Surface Topography of proteins
journal, July 2003
- Binkowski, T. A.
- Nucleic Acids Research, Vol. 31, Issue 13
Works referencing / citing this record:
A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
journal, January 2020
- Gsell, Corina; Richly, Holger; Coin, Frédéric
- Nucleic Acids Research, Vol. 48, Issue 4
A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
text, January 2020
- Gsell, Corina; Richly, Holger; Coin, Frédéric
- Oxford University Press