Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition
Abstract
Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein (HMCES) can covalently cross-link to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, in this paper, we report crystal structures of the human HMCES SOS response-associated peptidase (SRAP) domain in complex with DNA-damage substrates, including HMCES cross-linked with an abasic site within a 3' overhang DNA. HMCES interacts with both single-strand and duplex segments of DNA, with two independent duplex DNA interaction sites identified in the SRAP domain. The HMCES DNA-protein cross-link structure provides structural insights into a novel thiazolidine covalent interaction between the DNA abasic site and conserved Cys 2 of HMCES. Collectively, our structures demonstrate the capacity for the SRAP domain to interact with a variety of single-strand- and double-strand-containing DNA structures found in DNA-damage sites, including 5' and 3' overhang DNAs and gapped DNAs with short single-strand segments.
- Authors:
-
[1];
[1];
[4]
- Univ. of Toronto, ON (Canada)
- La Jolla Inst. for Immunology, CA (United States); Univ. of San Diego, La Jolla, CA (United States); Sanford Consortium for Regenerative Medicine, La Jolla, CA (United States)
- National Inst. of Health (NIH), Bethesda, MD (United States). National Center for Biotechnology Information and National Library of Medicine
- Univ. of Toronto, ON (Canada); University Health Network, Toronto, ON (Canada)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); Canadian Institutes of Health Research (CIHR); Natural Sciences and Engineering Research Council of Canada (NSERC); National Library of Medicine (NLM); National Cancer Institute (NCI)
- OSTI Identifier:
- 1543001
- Grant/Contract Number:
- AC02-05CH11231; AC02-06CH11357; S10 RR029205
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Structural & Molecular Biology
- Additional Journal Information:
- Journal Volume: 26; Journal Issue: 7; Journal ID: ISSN 1545-9993
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Base excision repair; X-ray crystallography
Citation Formats
Halabelian, Levon, Ravichandran, Mani, Li, Yanjun, Zeng, Hong, Rao, Anjana, Aravind, L., and Arrowsmith, Cheryl H. Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition. United States: N. p., 2019.
Web. doi:10.1038/s41594-019-0246-6.
Halabelian, Levon, Ravichandran, Mani, Li, Yanjun, Zeng, Hong, Rao, Anjana, Aravind, L., & Arrowsmith, Cheryl H. Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition. United States. https://doi.org/10.1038/s41594-019-0246-6
Halabelian, Levon, Ravichandran, Mani, Li, Yanjun, Zeng, Hong, Rao, Anjana, Aravind, L., and Arrowsmith, Cheryl H. Mon .
"Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition". United States. https://doi.org/10.1038/s41594-019-0246-6. https://www.osti.gov/servlets/purl/1543001.
@article{osti_1543001,
title = {Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition},
author = {Halabelian, Levon and Ravichandran, Mani and Li, Yanjun and Zeng, Hong and Rao, Anjana and Aravind, L. and Arrowsmith, Cheryl H.},
abstractNote = {Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein (HMCES) can covalently cross-link to abasic sites in single-stranded DNA at stalled replication forks to prevent genome instability. Here, in this paper, we report crystal structures of the human HMCES SOS response-associated peptidase (SRAP) domain in complex with DNA-damage substrates, including HMCES cross-linked with an abasic site within a 3' overhang DNA. HMCES interacts with both single-strand and duplex segments of DNA, with two independent duplex DNA interaction sites identified in the SRAP domain. The HMCES DNA-protein cross-link structure provides structural insights into a novel thiazolidine covalent interaction between the DNA abasic site and conserved Cys 2 of HMCES. Collectively, our structures demonstrate the capacity for the SRAP domain to interact with a variety of single-strand- and double-strand-containing DNA structures found in DNA-damage sites, including 5' and 3' overhang DNAs and gapped DNAs with short single-strand segments.},
doi = {10.1038/s41594-019-0246-6},
journal = {Nature Structural & Molecular Biology},
number = 7,
volume = 26,
place = {United States},
year = {2019},
month = {6}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 28 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Novel autoproteolytic and DNA-damage sensing components in the bacterial SOS response and oxidized methylcytosine-induced eukaryotic DNA demethylation systems
journal, August 2013
- Aravind, L.; Anand, Swadha; Iyer, Lakshminarayan M.
- Biology Direct, Vol. 8, Issue 1
Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives
journal, February 2013
- Spruijt, Cornelia G.; Gnerlich, Felix; Smits, Arne H.
- Cell, Vol. 152, Issue 5
The Curious Chemical Biology of Cytosine: Deamination, Methylation,and Oxidation as Modulators of Genomic Potential
journal, October 2011
- Nabel, Christopher S.; Manning, Sara A.; Kohli, Rahul M.
- ACS Chemical Biology, Vol. 7, Issue 1
Improvements to the APBS biomolecular solvation software suite: Improvements to the APBS Software Suite
journal, October 2017
- Jurrus, Elizabeth; Engel, Dave; Star, Keith
- Protein Science, Vol. 27, Issue 1
How good are my data and what is the resolution?
journal, June 2013
- Evans, Philip R.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
Overview of the CCP 4 suite and current developments
journal, March 2011
- Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures
journal, July 2005
- Landau, M.; Mayrose, I.; Rosenberg, Y.
- Nucleic Acids Research, Vol. 33, Issue Web Server
Replisome Dynamics and Their Functional Relevance upon DNA Damage through the PCNA Interactome
journal, December 2018
- Srivastava, Mrinal; Chen, Zhen; Zhang, Huimin
- Cell Reports, Vol. 25, Issue 13
HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA
journal, January 2019
- Mohni, Kareem N.; Wessel, Sarah R.; Zhao, Runxiang
- Cell, Vol. 176, Issue 1-2
Fisher's information in maximum-likelihood macromolecular crystallographic refinement
journal, November 2003
- Steiner, Roberto A.; Lebedev, Andrey A.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 59, Issue 12
Protection Against Acetaminophen Hepatotoxicity by Ribose-Cysteine (RibCys)
journal, April 1992
- Roberts, Jeanette C.; Charyulu, Rajeev L.; Zera, Richard T.
- Pharmacology & Toxicology, Vol. 70, Issue 4
Comparison of sequence profiles. Strategies for structural predictions using sequence information
journal, January 2000
- Rychlewski, Leszek; Li, Weizhong; Jaroszewski, Lukasz
- Protein Science, Vol. 9, Issue 2
Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA
journal, June 2013
- Iyer, Lakshminarayan M.; Zhang, Dapeng; Maxwell Burroughs, A.
- Nucleic Acids Research, Vol. 41, Issue 16
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Base excision repair of oxidative DNA damage and association with cancer and aging
journal, September 2008
- Maynard, S.; Schurman, S. H.; Harboe, C.
- Carcinogenesis, Vol. 30, Issue 1
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG
journal, November 2017
- Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W.
- Protein Science, Vol. 27, Issue 1
Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid.
journal, November 1989
- Hirel, P. H.; Schmitter, M. J.; Dessen, P.
- Proceedings of the National Academy of Sciences, Vol. 86, Issue 21
The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo
journal, February 2010
- Liu, M.; Bandaru, V.; Bond, J. P.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 11
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
DNA N-glycosidases: properties of uracil-DNA glycosidase from Escherichia coli.
journal, May 1977
- Lindahl, T.; Ljungquist, S.; Siegert, W.
- Journal of Biological Chemistry, Vol. 252, Issue 10
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019
- Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman
- Nature Communications, Vol. 10, Issue 1
Overview of the CCP4 suite and current developments.
text, January 2011
- Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
- Apollo - University of Cambridge Repository
Liquid chromatography mass spectrometry data of HMCES SRAP domain
dataset, January 2019
- Halabelian, Levon
- Zenodo
Improvements to the APBS biomolecular solvation software suite
text, January 2017
- Jurrus, Elizabeth; Engel, Dave; Star, Keith
- arXiv
Works referencing / citing this record:
Molecular basis of abasic site sensing in single-stranded DNA by the SRAP domain of E. coli yedK
journal, August 2019
- Wang, Na; Bao, Hongyu; Chen, Liu
- Nucleic Acids Research, Vol. 47, Issue 19