Visualizing functional dynamicity in the DNA-dependent protein kinase holoenzyme DNA-PK complex by integrating SAXS with cryo-EM

Hammel, Michal; Rosenberg, Daniel J.; Bierma, Jan; Hura, Gregory L.; Thapar, Roopa; Lees-Miller, Susan P.; Tainer, John A.

doi:10.1016/j.pbiomolbio.2020.09.003

Title: Visualizing functional dynamicity in the DNA-dependent protein kinase holoenzyme DNA-PK complex by integrating SAXS with cryo-EM

Journal Article · Sun Aug 01 00:00:00 EDT 2021 · Progress in Biophysics and Molecular Biology

DOI:https://doi.org/10.1016/j.pbiomolbio.2020.09.003· OSTI ID:1769492

; Rosenberg, Daniel J.; Bierma, Jan; Hura, Gregory L.; Thapar, Roopa; Lees-Miller, Susan P.; Tainer, John A.

Assembly of KU and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at DNA double strand breaks (DSBs) forms DNA-PK holoenzyme as a critical initiating step for non-homologous end joining (NHEJ) repair of DSBs produced by radiation and chemotherapies. Advanced cryo-electron microscopy (cryo-EM) imaging together with breakthrough macromolecular X-ray crystal (MX) structures of KU and DNA-PKcs recently enabled visualization of the ~600 kDa DNA-PK assembly at near atomic resolution. These important static structures provide the foundation for definition and interpretation of functional movements crucial to mechanistic understanding that can be tested through solution state structure analysis. We herein therefore leverage Cryo-EM and MX structures for the interpretation of synchrotron small-angle X-ray scattering (SAXS) data on DNA-PK conformations in solution to inform the structural mechanism for NHEJ initiation. SAXS, which measures thermodynamic solution-state conformational states and assemblies outside of cryo- and solid-state conditions, unveils the inherent flexibility of KU, DNA-PKcs and DNA-PK. The combined structural measurements reveal mobility of KU80 C-terminal region (KU80CTR), motion/plasticity of HEAT (DNA-PKcs Huntingtin, Elongation Factor 3, PP2 A, and TOR1) regions, allosteric switching upon DNA-PKcs autophosphorylation, and dimeric arrangements of DNA-PK assembly. Importantly, the results uncover displacement of the N-terminal HEAT domain during autophosphorylation as suitable for a regulated release mechanism of DNA-PKcs from DNA-PK to control unproductive access to toxic and mutagenic DNA repair intermediates. These integrated analyses show that the marriage of SAXS with cryo-EM leverages the strengths of both techniques to enable assessment of functional conformations and flexibility defining atomic-resolution molecular mechanisms for DSB repair.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Institute of General Medical Sciences

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1769492

Alternate ID(s):: OSTI ID: 1813417

Journal Information:: Progress in Biophysics and Molecular Biology, Journal Name: Progress in Biophysics and Molecular Biology Vol. 163 Journal Issue: C; ISSN 0079-6107

Publisher:: ElsevierCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (74)

Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase Bryant, Helen E.; Schultz, Niklas; Thomas, Huw D. Nature, Vol. 434, Issue 7035 https://doi.org/10.1038/nature03443	journal	April 2005
Kinetic Analysis of the Ku-DNA Binding Activity Reveals a Redox-dependent Alteration in Protein Structure That Stimulates Dissociation of the Ku-DNA Complex Andrews, Brooke J.; Lehman, Jason A.; Turchi, John J. Journal of Biological Chemistry, Vol. 281, Issue 19 https://doi.org/10.1074/jbc.M512787200	journal	May 2006
Modeling Structure and Dynamics of Protein Complexes with SAXS Profiles Schneidman-Duhovny, Dina; Hammel, Michal Protein Complex Assembly https://doi.org/10.1007/978-1-4939-7759-8_29	book	January 2018
PatchDock and SymmDock: servers for rigid and symmetric docking Schneidman-Duhovny, D.; Inbar, Y.; Nussinov, R. Nucleic Acids Research, Vol. 33, Issue Web Server https://doi.org/10.1093/nar/gki481	journal	July 2005
Geometry of a complex formed by double strand break repair proteins at a single DNA end: recruitment of DNA-PKcs induces inward translocation of Ku protein Yoo, S. Nucleic Acids Research, Vol. 27, Issue 24 https://doi.org/10.1093/nar/27.24.4679	journal	December 1999
Visualization of a DNA-PK/PARP1 complex Spagnolo, Laura; Barbeau, Jody; Curtin, Nicola J. Nucleic Acids Research, Vol. 40, Issue 9 https://doi.org/10.1093/nar/gkr1231	journal	January 2012
Organization and dynamics of the nonhomologous end-joining machinery during DNA double-strand break repair Reid, Dylan A.; Keegan, Sarah; Leo-Macias, Alejandra Proceedings of the National Academy of Sciences, Vol. 112, Issue 20 https://doi.org/10.1073/pnas.1420115112	journal	May 2015
Structural basis for AcrVA4 inhibition of specific CRISPR-Cas12a Knott, Gavin J.; Cress, Brady F.; Liu, Jun-Jie eLife, Vol. 8 https://doi.org/10.7554/eLife.49110	journal	August 2019
Structural insights into NHEJ: Building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time Williams, Gareth J.; Hammel, Michal; Radhakrishnan, Sarvan Kumar DNA Repair, Vol. 17 https://doi.org/10.1016/j.dnarep.2014.02.009	journal	May 2014
The DNA-Dependent Protein Kinase Catalytic Subunit Is Phosphorylated In Vivo on Threonine 3950, a Highly Conserved Amino Acid in the Protein Kinase Domain Douglas, Pauline; Cui, Xiaoping; Block, Wesley D. Molecular and Cellular Biology, Vol. 27, Issue 5 https://doi.org/10.1128/MCB.01962-06	journal	December 2006
XLF Regulates Filament Architecture of the XRCC4·Ligase IV Complex Hammel, Michal; Yu, Yaping; Fang, Shujuan Structure, Vol. 18, Issue 11 https://doi.org/10.1016/j.str.2010.09.009	journal	November 2010
XRCC4 Protein Interactions with XRCC4-like Factor (XLF) Create an Extended Grooved Scaffold for DNA Ligation and Double Strand Break Repair Hammel, Michal; Rey, Martial; Yu, Yaping Journal of Biological Chemistry, Vol. 286, Issue 37 https://doi.org/10.1074/jbc.M111.272641	journal	July 2011
Cryo-EM structure of the DNA-PK holoenzyme Sharif, Humayun; Li, Yang; Dong, Yuanchen Proceedings of the National Academy of Sciences, Vol. 114, Issue 28 https://doi.org/10.1073/pnas.1707386114	journal	June 2017
Autophosphorylation of DNA-Dependent Protein Kinase Regulates DNA End Processing and May Also Alter Double-Strand Break Repair Pathway Choice Cui, Xiaoping; Yu, Yaping; Gupta, Shikha Molecular and Cellular Biology, Vol. 25, Issue 24 https://doi.org/10.1128/MCB.25.24.10842-10852.2005	journal	December 2005
DNA-dependent protein kinase catalytic subunit: A relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product Hartley, Katharine O.; Gell, David; Smith, Graeme C. M. Cell, Vol. 82, Issue 5 https://doi.org/10.1016/0092-8674(95)90482-4	journal	September 1995
The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis Jette, Nicholas; Lees-Miller, Susan P. Progress in Biophysics and Molecular Biology, Vol. 117, Issue 2-3 https://doi.org/10.1016/j.pbiomolbio.2014.12.003	journal	March 2015
Envisioning the dynamics and flexibility of Mre11-Rad50-Nbs1 complex to decipher its roles in DNA replication and repair Lafrance-Vanasse, Julien; Williams, Gareth J.; Tainer, John A. Progress in Biophysics and Molecular Biology, Vol. 117, Issue 2-3 https://doi.org/10.1016/j.pbiomolbio.2014.12.004	journal	March 2015
Autophosphorylation of the Catalytic Subunit of the DNA-Dependent Protein Kinase Is Required for Efficient End Processing during DNA Double-Strand Break Repair Ding, Qi; Reddy, Yeturu V. R.; Wang, Wei Molecular and Cellular Biology, Vol. 23, Issue 16 https://doi.org/10.1128/MCB.23.16.5836-5848.2003	journal	August 2003
Cell Cycle Dependence of DNA-dependent Protein Kinase Phosphorylation in Response to DNA Double Strand Breaks Chen, Benjamin P. C.; Chan, Doug W.; Kobayashi, Junya Journal of Biological Chemistry, Vol. 280, Issue 15 https://doi.org/10.1074/jbc.M408827200	journal	April 2005
Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends Block, W. D. Nucleic Acids Research, Vol. 32, Issue 14 https://doi.org/10.1093/nar/gkh761	journal	August 2004
Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences Bacolla, Albino; Tainer, John A.; Vasquez, Karen M. Nucleic Acids Research, Vol. 44, Issue 12 https://doi.org/10.1093/nar/gkw261	journal	April 2016
Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death Houl, Jerry H.; Ye, Zu; Brosey, Chris A. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13508-4	journal	December 2019
X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution Putnam, Christopher D.; Hammel, Michal; Hura, Greg L. Quarterly Reviews of Biophysics, Vol. 40, Issue 3 https://doi.org/10.1017/S0033583507004635	journal	August 2007
Accurate SAXS Profile Computation and its Assessment by Contrast Variation Experiments Schneidman-Duhovny, Dina; Hammel, Michal; Tainer, John A. Biophysical Journal, Vol. 105, Issue 4 https://doi.org/10.1016/j.bpj.2013.07.020	journal	August 2013
The MRE11–RAD50–NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair Syed, Aleem; Tainer, John A. Annual Review of Biochemistry, Vol. 87, Issue 1 https://doi.org/10.1146/annurev-biochem-062917-012415	journal	June 2018
Super-Resolution in Solution X-Ray Scattering and Its Applications to Structural Systems Biology Rambo, Robert P.; Tainer, John A. Annual Review of Biophysics, Vol. 42, Issue 1 https://doi.org/10.1146/annurev-biophys-083012-130301	journal	May 2013
Structures of closed and open conformations of dimeric human ATM Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I. Science Advances, Vol. 3, Issue 5 https://doi.org/10.1126/sciadv.1700933	journal	May 2017
FoXS, FoXSDock and MultiFoXS: Single-state and multi-state structural modeling of proteins and their complexes based on SAXS profiles Schneidman-Duhovny, Dina; Hammel, Michal; Tainer, John A. Nucleic Acids Research, Vol. 44, Issue W1 https://doi.org/10.1093/nar/gkw389	journal	May 2016
Dissection of DNA double-strand-break repair using novel single-molecule forceps Wang, Jing L.; Duboc, Camille; Wu, Qian Nature Structural & Molecular Biology, Vol. 25, Issue 6 https://doi.org/10.1038/s41594-018-0065-1	journal	May 2018
Cryo-EM structure of human DNA-PK holoenzyme Yin, Xiaotong; Liu, Mengjie; Tian, Yuan Cell Research, Vol. 27, Issue 11 https://doi.org/10.1038/cr.2017.110	journal	August 2017
DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities Shibata, Atsushi; Moiani, Davide; Arvai, Andrew S. Molecular Cell, Vol. 53, Issue 1 https://doi.org/10.1016/j.molcel.2013.11.003	journal	January 2014
Phosphate steering by Flap Endonuclease 1 promotes 5′-flap specificity and incision to prevent genome instability Tsutakawa, Susan E.; Thompson, Mark J.; Arvai, Andrew S. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15855	journal	June 2017
Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase Douglas, Pauline; Sapkota, Gopal P.; Morrice, Nick Biochemical Journal, Vol. 368, Issue 1 https://doi.org/10.1042/bj20020973	journal	November 2002
Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS) Hura, Greg L.; Menon, Angeli L.; Hammel, Michal Nature Methods, Vol. 6, Issue 8 https://doi.org/10.1038/nmeth.1353	journal	July 2009
Deciphering conformational transitions of proteins by small angle X-ray scattering and normal mode analysis Panjkovich, Alejandro; Svergun, Dmitri I. Physical Chemistry Chemical Physics, Vol. 18, Issue 8 https://doi.org/10.1039/C5CP04540A	journal	January 2016
Validation of macromolecular flexibility in solution by small-angle X-ray scattering (SAXS) Hammel, Michal European Biophysics Journal, Vol. 41, Issue 10 https://doi.org/10.1007/s00249-012-0820-x	journal	May 2012
DNA requirements for interaction of the C-terminal region of Ku80 with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) Radhakrishnan, Sarvan Kumar; Lees-Miller, Susan P. DNA Repair, Vol. 57 https://doi.org/10.1016/j.dnarep.2017.06.001	journal	September 2017
Three-Dimensional Structure of the Human DNA-PKcs/Ku70/Ku80 Complex Assembled on DNA and Its Implications for DNA DSB Repair Spagnolo, Laura; Rivera-Calzada, Angel; Pearl, Laurence H. Molecular Cell, Vol. 22, Issue 4 https://doi.org/10.1016/j.molcel.2006.04.013	journal	May 2006
Ku and DNA-dependent Protein Kinase Dynamic Conformations and Assembly Regulate DNA Binding and the Initial Non-homologous End Joining Complex Hammel, Michal; Yu, Yaping; Mahaney, Brandi L. Journal of Biological Chemistry, Vol. 285, Issue 2 https://doi.org/10.1074/jbc.M109.065615	journal	November 2009
Comparative Protein Modelling by Satisfaction of Spatial Restraints Šali, Andrej; Blundell, Tom L. Journal of Molecular Biology, Vol. 234, Issue 3 https://doi.org/10.1006/jmbi.1993.1626	journal	December 1993
Implementation and performance of SIBYLS: a dual endstation small-angle X-ray scattering and macromolecular crystallography beamline at the Advanced Light Source Classen, Scott; Hura, Greg L.; Holton, James M. Journal of Applied Crystallography, Vol. 46, Issue 1 https://doi.org/10.1107/S0021889812048698	journal	January 2013
Mechanism of DNA End Sensing and Processing by the Mre11-Rad50 Complex Käshammer, Lisa; Saathoff, Jan-Hinnerk; Lammens, Katja Molecular Cell, Vol. 76, Issue 3 https://doi.org/10.1016/j.molcel.2019.07.035	journal	November 2019
Evolving SAXS versatility: solution X-ray scattering for macromolecular architecture, functional landscapes, and integrative structural biology Brosey, Chris A.; Tainer, John A. Current Opinion in Structural Biology, Vol. 58 https://doi.org/10.1016/j.sbi.2019.04.004	journal	October 2019
Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta Chan, Doug W.; Ting, Nicholas S. Y.; Lees-Miller, Susan P. Biochemistry and Cell Biology, Vol. 74, Issue 1 https://doi.org/10.1139/o96-007	journal	January 1996
High-Throughput SAXS for the Characterization of Biomolecules in Solution: A Practical Approach Dyer, Kevin N.; Hammel, Michal; Rambo, Robert P. Structural Genomics https://doi.org/10.1007/978-1-62703-691-7_18	book	October 2013
FoXS: a web server for rapid computation and fitting of SAXS profiles Schneidman-Duhovny, D.; Hammel, M.; Sali, A. Nucleic Acids Research, Vol. 38, Issue Web Server https://doi.org/10.1093/nar/gkq461	journal	May 2010
Detection and Repair of Ionizing Radiation-Induced DNA Double Strand Breaks: New Developments in Nonhomologous End Joining Wang, Chen; Lees-Miller, Susan P. International Journal of Radiation OncologyBiologyPhysics, Vol. 86, Issue 3 https://doi.org/10.1016/j.ijrobp.2013.01.011	journal	July 2013
Site-specific proteolytic cleavage of Ku protein bound to DNA Paillard, Sophie; Strauss, François Proteins: Structure, Function, and Genetics, Vol. 15, Issue 3 https://doi.org/10.1002/prot.340150310	journal	March 1993
Flexible Tethering of ASPP Proteins Facilitates PP-1c Catalysis Zhou, Yeyun; Millott, Robyn; Kim, Hyeong Jin Structure, Vol. 27, Issue 10 https://doi.org/10.1016/j.str.2019.07.012	journal	October 2019
Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs Boskovic, J. The EMBO Journal, Vol. 22, Issue 21 https://doi.org/10.1093/emboj/cdg555	journal	November 2003
Comprehensive macromolecular conformations mapped by quantitative SAXS analyses Hura, Greg L.; Budworth, Helen; Dyer, Kevin N. Nature Methods, Vol. 10, Issue 6 https://doi.org/10.1038/nmeth.2453	journal	April 2013
Mapping of protein-protein interactions within the DNA-dependent protein kinase complex Gell, D.; Jackson, S. P. Nucleic Acids Research, Vol. 27, Issue 17 https://doi.org/10.1093/nar/27.17.3494	journal	September 1999
Chromosomal Translocations in Human Cells Are Generated by Canonical Nonhomologous End-Joining Ghezraoui, Hind; Piganeau, Marion; Renouf, Benjamin Molecular Cell, Vol. 55, Issue 6 https://doi.org/10.1016/j.molcel.2014.08.002	journal	September 2014
Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats Sibanda, Bancinyane L.; Chirgadze, Dimitri Y.; Blundell, Tom L. Nature, Vol. 463, Issue 7277 https://doi.org/10.1038/nature08648	journal	December 2009
A noncatalytic function of the ligation complex during nonhomologous end joining Cottarel, Jessica; Frit, Philippe; Bombarde, Oriane The Journal of Cell Biology, Vol. 200, Issue 2 https://doi.org/10.1083/jcb.201203128	journal	January 2013
DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals Hura, G. L.; Tsai, C. -L.; Claridge, S. A. Proceedings of the National Academy of Sciences, Vol. 110, Issue 43 https://doi.org/10.1073/pnas.1308595110	journal	October 2013
Noncoding RNA joins Ku and DNA-PKcs for DNA-break resistance in breast cancer Lees-Miller, Susan P.; Beattie, Tara L.; Tainer, John A. Nature Structural & Molecular Biology, Vol. 23, Issue 6 https://doi.org/10.1038/nsmb.3240	journal	June 2016
Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks Uematsu, Naoya; Weterings, Eric; Yano, Ken-ichi Journal of Cell Biology, Vol. 177, Issue 2 https://doi.org/10.1083/jcb.200608077	journal	April 2007
Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40 Yang, Haijuan; Jiang, Xiaolu; Li, Buren Nature, Vol. 552, Issue 7685 https://doi.org/10.1038/nature25023	journal	December 2017
Cryo-EM Structure of the DNA-Dependent Protein Kinase Catalytic Subunit at Subnanometer Resolution Reveals α Helices and Insight into DNA Binding Williams, Dewight R.; Lee, Kyung-Jong; Shi, Jian Structure, Vol. 16, Issue 3 https://doi.org/10.1016/j.str.2007.12.014	journal	March 2008
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair Walker, John R.; Corpina, Richard A.; Goldberg, Jonathan Nature, Vol. 412, Issue 6847 https://doi.org/10.1038/35088000	journal	August 2001
Biochemical characterization of the ataxia-telangiectasia mutated (ATM) protein from human cells Goodarzi, Aaron A.; Lees-Miller, Susan P. DNA Repair, Vol. 3, Issue 7 https://doi.org/10.1016/j.dnarep.2004.03.041	journal	July 2004
An Intrinsically Disordered APLF Links Ku, DNA-PKcs, and XRCC4-DNA Ligase IV in an Extended Flexible Non-homologous End Joining Complex Hammel, Michal; Yu, Yaping; Radhakrishnan, Sarvan K. Journal of Biological Chemistry, Vol. 291, Issue 53 https://doi.org/10.1074/jbc.M116.751867	journal	December 2016
Characterizing flexible and intrinsically unstructured biological macromolecules by SAS using the Porod-Debye law Rambo, Robert P.; Tainer, John A. Biopolymers, Vol. 95, Issue 8 https://doi.org/10.1002/bip.21638	journal	April 2011
Structure and flexibility within proteins as identified through small angle X-ray scattering Pelikan, M.; Hura, G.; Hammel, M. General Physiology and Biophysics, Vol. 28, Issue 2 https://doi.org/10.4149/gpb_2009_02_174	journal	January 2009
Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR Baretic, Domagoj; Maia de Oliveira, Taiana; Niess, Martina Progress in Biophysics and Molecular Biology, Vol. 147 https://doi.org/10.1016/j.pbiomolbio.2019.06.003	journal	October 2019
Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy Horst, Benjamin G.; Yokom, Adam L.; Rosenberg, Daniel J. eLife, Vol. 8 https://doi.org/10.7554/eLife.50634	journal	September 2019
Three-Dimensional Structure and Regulation of the DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs) Rivera-Calzada, Angel; Maman, Joseph P.; Spagnolo, Laura Structure, Vol. 13, Issue 2 https://doi.org/10.1016/j.str.2004.12.006	journal	February 2005
Live cell imaging of XLF and XRCC4 reveals a novel view of protein assembly in the non-homologous end-joining pathway Yano, Ken-ichi; Chen, David J. Cell Cycle, Vol. 7, Issue 10 https://doi.org/10.4161/cc.7.10.5898	journal	May 2008
Accurate assessment of mass, models and resolution by small-angle scattering Rambo, Robert P.; Tainer, John A. Nature, Vol. 496, Issue 7446 https://doi.org/10.1038/nature12070	journal	April 2013
Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations Tsutakawa, Susan E.; Sarker, Altaf H.; Ng, Clifford Proceedings of the National Academy of Sciences, Vol. 117, Issue 25 https://doi.org/10.1073/pnas.1921311117	journal	June 2020
Structural model of full‐length human Ku70–Ku80 heterodimer and its recognition of DNA and DNA‐PKcs Rivera‐Calzada, Angel; Spagnolo, Laura; Pearl, Laurence H. EMBO reports, Vol. 8, Issue 1 https://doi.org/10.1038/sj.embor.7400847	journal	December 2006
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair Sibanda, Bancinyane L.; Chirgadze, Dimitri Y.; Ascher, David B. Science, Vol. 355, Issue 6324 https://doi.org/10.1126/science.aak9654	journal	February 2017
The 3D Solution Structure of the C-terminal Region of Ku86 (Ku86CTR) Harris, Richard; Esposito, Diego; Sankar, Andrew Journal of Molecular Biology, Vol. 335, Issue 2 https://doi.org/10.1016/j.jmb.2003.10.047	journal	January 2004

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59 BASIC BIOLOGICAL SCIENCES
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Cryo-electron microscopy
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Title: Visualizing functional dynamicity in the DNA-dependent protein kinase holoenzyme DNA-PK complex by integrating SAXS with cryo-EM

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