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; Mani, Rajam S.; Classen, Scott; Liu, Mona; Pique, Michael E.; Fang, Shujuan; Mahaney, Brandi L.; Weinfeld, Michael; Schriemer, David C.; Lees-Miller, Susan P.; Tainer, John A.

doi:10.1074/jbc.m111.272641

XRCC4 Protein Interactions with XRCC4-like Factor (XLF) Create an Extended Grooved Scaffold for DNA Ligation and Double Strand Break Repair

Journal Article · Wed Jul 20 00:00:00 EDT 2011 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.m111.272641· OSTI ID:1625074

Hammel, Michal ^[1]; Rey, Martial ^[2]; Yu, Yaping ^[2]; Mani, Rajam S. ^[3]; Classen, Scott ^[4]; Liu, Mona ^[4]; Pique, Michael E. ^[5]; Fang, Shujuan ^[2]; Mahaney, Brandi L. ^[2]; Weinfeld, Michael ^[3]; Schriemer, David C. ^[2]; Lees-Miller, Susan P. ^[2]; Tainer, John A. ^[6]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; DOE/OSTI
Univ. of Calgary, AB (Canada). Southern Alberta Cancer Research Inst. Dept. of Biochemistry and Molecular Biology
Univ. of Calgary, AB (Canada). Cross Cancer Inst. Dept. of Oncology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division
The Scripps Research Inst., La Jolla, CA (United States). Skaggs Inst. of Chemical Biology. Dept. of Molecular Biology
The Scripps Research Inst., La Jolla, CA (United States). Skaggs Inst. of Chemical Biology. Dept. of Molecular Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division

The XRCC4-like factor (XLF)-XRCC4 complex is essential for nonhomologous end joining, the major repair pathway for DNA double strand breaks in human cells. Yet, how XLF binds XRCC4 and impacts nonhomologous end joining functions has been enigmatic. Here, we report the XLF-XRCC4 complex crystal structure in combination with biophysical and mutational analyses to define the XLF-XRCC4 interactions. Crystal and solution structures plus mutations characterize alternating XRCC4 and XLF head domain interfaces forming parallel superhelical filaments. XLF Leu-115 (“Leu-lock”) inserts into a hydrophobic pocket formed by XRCC4 Met-59, Met-61, Lys-65, Lys99, Phe-106, and Leu-108 in synergy with pseudo-symmetric -zipper hydrogen bonds to drive specificity. XLF C terminus and DNA enhance parallel filament formation. Super-helical XLF-XRCC4 filaments form a positively charged channel to bind DNA and align ends for efficient ligation. Collective results reveal how human XLF and XRCC4 interact to bind DNA, suggest consequences of patient mutations, and support a unified molecular mechanism for XLF-XRCC4 stimulation of DNA ligation.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625074

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 37 Vol. 286; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (61)

DNA Double-Strand Break Repair: A Relentless Hunt Uncovers New Prey Sekiguchi, JoAnn M.; Ferguson, David O. Cell, Vol. 124, Issue 2 https://doi.org/10.1016/j.cell.2006.01.010	journal	January 2006
Human Flap Endonuclease Structures, DNA Double-Base Flipping, and a Unified Understanding of the FEN1 Superfamily Tsutakawa, Susan E.; Classen, Scott; Chapados, Brian R. Cell, Vol. 145, Issue 2 https://doi.org/10.1016/j.cell.2011.03.004	journal	April 2011
DNA-PK and ATM phosphorylation sites in XLF/Cernunnos are not required for repair of DNA double strand breaks Yu, Y.; Mahaney, B.; Yano, K. DNA Repair, Vol. 7, Issue 10 https://doi.org/10.1016/j.dnarep.2008.06.015	journal	October 2008
A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation Dobbs, Tracey A.; Tainer, John A.; Lees-Miller, Susan P. DNA Repair, Vol. 9, Issue 12 https://doi.org/10.1016/j.dnarep.2010.09.019	journal	December 2010
Functional significance of the interaction with Ku in DNA double-strand break recognition of XLF Yano, Ken-ichi; Morotomi-Yano, Keiko; Lee, Kyung-Jong FEBS Letters, Vol. 585, Issue 6 https://doi.org/10.1016/j.febslet.2011.02.020	journal	February 2011
Crystal Structure of Human XLF: A Twist in Nonhomologous DNA End-Joining Andres, Sara N.; Modesti, Mauro; Tsai, Chun J. Molecular Cell, Vol. 28, Issue 6 https://doi.org/10.1016/j.molcel.2007.10.024	journal	December 2007
The DNA Damage Response: Making It Safe to Play with Knives Ciccia, Alberto; Elledge, Stephen J. Molecular Cell, Vol. 40, Issue 2 https://doi.org/10.1016/j.molcel.2010.09.019	journal	October 2010
Bridging the solution divide: comprehensive structural analyses of dynamic RNA, DNA, and protein assemblies by small-angle X-ray scattering Rambo, Robert P.; Tainer, John A. Current Opinion in Structural Biology, Vol. 20, Issue 1 https://doi.org/10.1016/j.sbi.2009.12.015	journal	February 2010
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
Human DNA Ligase III Recognizes DNA Ends by Dynamic Switching between Two DNA-Bound States Cotner-Gohara, Elizabeth; Kim, In-Kwon; Hammel, Michal Biochemistry, Vol. 49, Issue 29 https://doi.org/10.1021/bi100503w	journal	July 2010
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
Human DNA ligase I completely encircles and partially unwinds nicked DNA Pascal, John M.; O'Brien, Patrick J.; Tomkinson, Alan E. Nature, Vol. 432, Issue 7016 https://doi.org/10.1038/nature03082	journal	November 2004
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
Molecular mimicry of SUMO promotes DNA repair Prudden, John; Perry, J. Jefferson P.; Arvai, Andrew S. Nature Structural & Molecular Biology, Vol. 16, Issue 5 https://doi.org/10.1038/nsmb.1582	journal	April 2009
SUMO-targeted ubiquitin ligases in genome stability Prudden, John; Pebernard, Stephanie; Raffa, Grazia The EMBO Journal, Vol. 26, Issue 18 https://doi.org/10.1038/sj.emboj.7601838	journal	August 2007
Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ Li, Yi; Chirgadze, Dimitri Y.; Bolanos-Garcia, Victor M. The EMBO Journal, Vol. 27, Issue 1 https://doi.org/10.1038/sj.emboj.7601942	journal	November 2007
Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends Tsai, C. J.; Kim, S. A.; Chu, G. Proceedings of the National Academy of Sciences, Vol. 104, Issue 19 https://doi.org/10.1073/pnas.0702620104	journal	April 2007
Evolutionary and Functional Conservation of the DNA Non-homologous End-joining Protein, XLF/Cernunnos* Hentges, Pierre; Ahnesorg, Peter; Pitcher, Robert S. Journal of Biological Chemistry, Vol. 281, Issue 49 https://doi.org/10.1074/jbc.m608727200	journal	December 2006
Length-dependent Binding of Human XLF to DNA and Stimulation of XRCC4·DNA Ligase IV Activity* Lu, Haihui; Pannicke, Ulrich; Schwarz, Klaus Journal of Biological Chemistry, Vol. 282, Issue 15 https://doi.org/10.1074/jbc.m609904200	journal	April 2007
DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner Park, E. -J. Nucleic Acids Research, Vol. 31, Issue 23 https://doi.org/10.1093/nar/gkg921	journal	December 2003
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/s0021889807021206	journal	July 2007
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/s0907444904019158	journal	November 2004
The C-Terminal Domain of Cernunnos/XLF Is Dispensable for DNA Repair In Vivo Malivert, Laurent; Callebaut, Isabelle; Rivera-Munoz, Paola Molecular and Cellular Biology, Vol. 29, Issue 5 https://doi.org/10.1128/mcb.01521-08	journal	December 2008
Eukaryotic DNA Ligases: Structural and Functional Insights Ellenberger, Tom; Tomkinson, Alan E. Annual Review of Biochemistry, Vol. 77, Issue 1 https://doi.org/10.1146/annurev.biochem.77.061306.123941	journal	June 2008
Loading of the Nonhomologous End Joining Factor, Ku, on Protein-occluded DNA Ends A., Roberts, Steven; A., Ramsden, Dale The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/qc4b-cx28	text	January 2007
Dual Modes of Interaction between XRCC4 and Polynucleotide Kinase/Phosphatase: IMPLICATIONS FOR NONHOMOLOGOUS END JOINING A., Ramsden, Dale; Shujuan, Fang,; Mesfin, Fanta, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/zpb0-8490	text	January 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats. Sibanda, Lynn; Chirgadze, Dima; Blundell, Tom Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.65857	text	January 2010
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
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
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Cernunnos, a Novel Nonhomologous End-Joining Factor, Is Mutated in Human Immunodeficiency with Microcephaly Buck, Dietke; Malivert, Laurent; de Chasseval, Régina Cell, Vol. 124, Issue 2 https://doi.org/10.1016/j.cell.2005.12.030	journal	January 2006
XLF Interacts with the XRCC4-DNA Ligase IV Complex to Promote DNA Nonhomologous End-Joining Ahnesorg, Peter; Smith, Philippa; Jackson, Stephen P. Cell, Vol. 124, Issue 2 https://doi.org/10.1016/j.cell.2005.12.031	journal	January 2006
DNA base damage recognition and removal: New twists and grooves Huffman, Joy L.; Sundheim, Ottar; Tainer, John A. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 577, Issue 1-2 https://doi.org/10.1016/j.mrfmmm.2005.03.012	journal	September 2005
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
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
Flipping of alkylated DNA damage bridges base and nucleotide excision repair Tubbs, Julie L.; Latypov, Vitaly; Kanugula, Sreenivas Nature, Vol. 459, Issue 7248 https://doi.org/10.1038/nature08076	journal	June 2009
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
Crystal structure of an Xrcc4–DNA ligase IV complex Sibanda, Bancinyane L.; Critchlow, Susan E.; Begun, Jake Nature Structural Biology, Vol. 8, Issue 12, p. 1015-1019 https://doi.org/10.1038/nsb725	journal	November 2001
NHEJ and its backup pathways in chromosomal translocations Lieber, Michael R. Nature Structural & Molecular Biology, Vol. 17, Issue 4 https://doi.org/10.1038/nsmb0410-393	journal	April 2010
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
Ku recruits XLF to DNA double-strand breaks Yano, Ken-ichi; Morotomi-Yano, Keiko; Wang, Shih-Ya EMBO reports, Vol. 9, Issue 1 https://doi.org/10.1038/sj.embor.7401137	journal	December 2007
Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining Mahaney, Brandi L.; Meek, Katheryn; Lees-Miller, Susan P. Biochemical Journal, Vol. 417, Issue 3 https://doi.org/10.1042/BJ20080413	journal	January 2009
Dual Modes of Interaction between XRCC4 and Polynucleotide Kinase/Phosphatase: IMPLICATIONS FOR NONHOMOLOGOUS END JOINING Mani, Rajam S.; Yu, Yaping; Fang, Shujuan Journal of Biological Chemistry, Vol. 285, Issue 48 https://doi.org/10.1074/jbc.M109.058719	journal	September 2010
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
Delineation of the Xrcc4-interacting Region in the Globular Head Domain of Cernunnos/XLF* Malivert, Laurent; Ropars, Virginie; Nunez, Marcela Journal of Biological Chemistry, Vol. 285, Issue 34 https://doi.org/10.1074/jbc.M110.138156	journal	August 2010
Evolutionary and Functional Conservation of the DNA Non-homologous End-joining Protein, XLF/Cernunnos* Hentges, Pierre; Ahnesorg, Peter; Pitcher, Robert S. Journal of Biological Chemistry, Vol. 281, Issue 49 https://doi.org/10.1074/jbc.M608727200	journal	December 2006
Length-dependent Binding of Human XLF to DNA and Stimulation of XRCC4·DNA Ligase IV Activity* Lu, Haihui; Pannicke, Ulrich; Schwarz, Klaus Journal of Biological Chemistry, Vol. 282, Issue 15 https://doi.org/10.1074/jbc.M609904200	journal	April 2007
Loading of the Nonhomologous End Joining Factor, Ku, on Protein-occluded DNA Ends Roberts, Steven A.; Ramsden, Dale A. Journal of Biological Chemistry, Vol. 282, Issue 14 https://doi.org/10.1074/jbc.M611125200	journal	April 2007
Crystal structure of the Xrcc4 DNA repair protein and implications for end joining Junop, M. S. The EMBO Journal, Vol. 19, Issue 22 https://doi.org/10.1093/emboj/19.22.5962	journal	November 2000
XLF-Cernunnos promotes DNA ligase IV–XRCC4 re-adenylation following ligation Riballo, Enriqueta; Woodbine, Lisa; Stiff, Thomas Nucleic Acids Research, Vol. 37, Issue 2 https://doi.org/10.1093/nar/gkn957	journal	December 2008
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
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering Franke, Daniel; Svergun, Dmitri I. Journal of Applied Crystallography, Vol. 42, Issue 2, p. 342-346 https://doi.org/10.1107/S0021889809000338	journal	January 2009
Determination of the regularization parameter in indirect-transform methods using perceptual criteria Svergun, D. I. Journal of Applied Crystallography, Vol. 25, Issue 4, p. 495-503 https://doi.org/10.1107/S0021889892001663	journal	August 1992
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Software for the high-throughput collection of SAXS data using an enhanced Blu-Ice / DCS control system Classen, Scott; Rodic, Ivan; Holton, James Journal of Synchrotron Radiation, Vol. 17, Issue 6 https://doi.org/10.1107/S0909049510028566	journal	September 2010
The C-Terminal Domain of Cernunnos/XLF Is Dispensable for DNA Repair In Vivo Malivert, Laurent; Callebaut, Isabelle; Rivera-Munoz, Paola Molecular and Cellular Biology, Vol. 29, Issue 5 https://doi.org/10.1128/MCB.01521-08	journal	December 2008
Structural and Functional Interaction between the Human DNA Repair Proteins DNA Ligase IV and XRCC4 Wu, P. -Y.; Frit, P.; Meesala, S. Molecular and Cellular Biology, Vol. 29, Issue 11 https://doi.org/10.1128/MCB.01895-08	journal	March 2009
Improving small-angle X-ray scattering data for structural analyses of the RNA world Rambo, R. P.; Tainer, J. A. RNA, Vol. 16, Issue 3 https://doi.org/10.1261/rna.1946310	journal	January 2010

Cited By (51)

Glyceryl ether, wax ester and triglyceride composition of the mouse preputial gland Sansone, Gail; Hamilton, James G. Lipids, Vol. 4, Issue 6 https://doi.org/10.1007/bf02531019	journal	November 1969
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
Achieving selectivity in space and time with DNA double-strand-break response and repair: molecular stages and scaffolds come with strings attached Liang, S.; Esswein, S. R.; Ochi, T. Structural Chemistry, Vol. 28, Issue 1 https://doi.org/10.1007/s11224-016-0841-7	journal	September 2016
Structural Basis of DNA Ligase IV-Artemis Interaction in Nonhomologous End-Joining De Ioannes, Pablo; Malu, Shruti; Cortes, Patricia Cell Reports, Vol. 2, Issue 6 https://doi.org/10.1016/j.celrep.2012.11.004	journal	December 2012
A Versatile Scaffold Contributes to Damage Survival via Sumoylation and Nuclease Interactions Sarangi, Prabha; Altmannova, Veronika; Holland, Cory Cell Reports, Vol. 9, Issue 1 https://doi.org/10.1016/j.celrep.2014.08.054	journal	October 2014
Non-homologous end joining: Emerging themes and unanswered questions Radhakrishnan, Sarvan Kumar; Jette, Nicholas; Lees-Miller, Susan P. DNA Repair, Vol. 17 https://doi.org/10.1016/j.dnarep.2014.01.009	journal	May 2014
The RAG recombinase: Beyond breaking Lescale, Chloé; Deriano, Ludovic Mechanisms of Ageing and Development, Vol. 165 https://doi.org/10.1016/j.mad.2016.11.003	journal	July 2017
Plugged into the Ku-DNA hub: The NHEJ network Frit, Philippe; Ropars, Virginie; Modesti, Mauro Progress in Biophysics and Molecular Biology, Vol. 147 https://doi.org/10.1016/j.pbiomolbio.2019.03.001	journal	October 2019
Structural Insights into the Role of Domain Flexibility in Human DNA Ligase IV Ochi, Takashi; Wu, Qian; Chirgadze, Dimitri Y. Structure, Vol. 20, Issue 7 https://doi.org/10.1016/j.str.2012.04.012	journal	July 2012
RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair Lescale, Chloé; Abramowski, Vincent; Bedora-Faure, Marie Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms10529	journal	February 2016
Stabilizing synapsis Song, Yiyun Nature Chemical Biology, Vol. 14, Issue 7 https://doi.org/10.1038/s41589-018-0095-3	journal	June 2018
A single XLF dimer bridges DNA ends during nonhomologous end joining Graham, Thomas G. W.; Carney, Sean M.; Walter, Johannes C. Nature Structural & Molecular Biology, Vol. 25, Issue 9 https://doi.org/10.1038/s41594-018-0120-y	journal	September 2018
Cooperative Assembly of a Protein-DNA Filament for Nonhomologous End Joining Tsai, Chun J.; Chu, Gilbert Journal of Biological Chemistry, Vol. 288, Issue 25 https://doi.org/10.1074/jbc.m113.464115	journal	June 2013
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
XRCC4's interaction with XLF is required for coding (but not signal) end joining Roy, S.; Andres, S. N.; Vergnes, A. Nucleic Acids Research, Vol. 40, Issue 4 https://doi.org/10.1093/nar/gkr1315	journal	January 2012
A human XRCC4–XLF complex bridges DNA Andres, Sara N.; Vergnes, Alexandra; Ristic, Dejan Nucleic Acids Research, Vol. 40, Issue 4 https://doi.org/10.1093/nar/gks022	journal	January 2012
ModBase, a database of annotated comparative protein structure models and associated resources Pieper, Ursula; Webb, Benjamin M.; Dong, Guang Qiang Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt1144	journal	November 2013
SFPQ•NONO and XLF function separately and together to promote DNA double-strand break repair via canonical nonhomologous end joining Jaafar, Lahcen; Li, Zhentian; Li, Shuyi Nucleic Acids Research, Vol. 45, Issue 4 https://doi.org/10.1093/nar/gkw1209	journal	December 2016
DNA repair factor APLF acts as a H2A-H2B histone chaperone through binding its DNA interaction surface Corbeski, Ivan; Dolinar, Klemen; Wienk, Hans Nucleic Acids Research, Vol. 46, Issue 14 https://doi.org/10.1093/nar/gky507	journal	June 2018
XRCC4/XLF Interaction Is Variably Required for DNA Repair and Is Not Required for Ligase IV Stimulation Roy, Sunetra; de Melo, Abinadabe J.; Xu, Yao Molecular and Cellular Biology, Vol. 35, Issue 17 https://doi.org/10.1128/mcb.01503-14	journal	September 2015
Integrative structural modeling with small angle X-ray scattering profiles Schneidman-Duhovny, Dina; Kim, Seung; Sali, Andrej BMC Structural Biology, Vol. 12, Issue 1 https://doi.org/10.1186/1472-6807-12-17	journal	January 2012
Resolution of complex ends by Nonhomologous end joining - better to be lucky than good? Strande, Natasha Tiffany; Waters, Crystal Ann; Ramsden, Dale A. Genome Integrity, Vol. 3, Issue 1 https://doi.org/10.1186/2041-9414-3-10	journal	January 2012
XLF-mediated NHEJ activity in hepatocellular carcinoma therapy resistance Yang, Sitian; Wang, Xiao Qi BMC Cancer, Vol. 17, Issue 1 https://doi.org/10.1186/s12885-017-3345-y	journal	May 2017
Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4 Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki PLoS Genetics, Vol. 10, Issue 8 https://doi.org/10.1371/journal.pgen.1004563	journal	August 2014
Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination. Lescale, Chloé; Lenden Hasse, Hélène; Blackford, Andrew N. Elsevier BV https://doi.org/10.17863/cam.6109	journalarticle	January 2016
Identification Of Natural Compound Derivative For Inhibition Of XLF And Overcoming Chemoresistance In Colorectal Cancer Cells Liu, Zhuo; Yu, Miao; Fei, Bingyuan Drug Design, Development and Therapy, Vol. Volume 13 https://doi.org/10.2147/dddt.s215967	journal	November 2019
Integration of DNA Damage and Repair with Murine Double-Minute 2 (Mdm2) in Tumorigenesis Lehman, Jason; Mayo, Lindsey International Journal of Molecular Sciences, Vol. 13, Issue 12 https://doi.org/10.3390/ijms131216373	journal	December 2012
The Expression Levels of XLF and Mutant P53 Are Inversely Correlated in Head and Neck Cancer Cells Feng, Sizhe; Rabii, Ramin; Liang, Guobiao Journal of Cancer, Vol. 7, Issue 11 https://doi.org/10.7150/jca.14669	journal	January 2016
Mutational phospho-mimicry reveals a regulatory role for the XRCC4 and XLF C-terminal tails in modulating DNA bridging during classical non-homologous end joining Normanno, Davide; Négrel, Aurélie; de Melo, Abinadabe J. eLife, Vol. 6 https://doi.org/10.7554/elife.22900	journal	May 2017
Mechanisms of DNA damage, repair, and mutagenesis: DNA Damage and Repair Chatterjee, Nimrat; Walker, Graham C. Environmental and Molecular Mutagenesis, Vol. 58, Issue 5 https://doi.org/10.1002/em.22087	journal	May 2017
DOT2: Macromolecular docking with improved biophysical models Roberts, Victoria A.; Thompson, Elaine E.; Pique, Michael E. Journal of Computational Chemistry, Vol. 34, Issue 20 https://doi.org/10.1002/jcc.23304	journal	May 2013
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
Role of non-homologous end joining in V(D)J recombination Malu, Shruti; Malshetty, Vidyasagar; Francis, Dailia Immunologic Research, Vol. 54, Issue 1-3 https://doi.org/10.1007/s12026-012-8329-z	journal	May 2012
Sliding sleeves of XRCC4–XLF bridge DNA and connect fragments of broken DNA Brouwer, Ineke; Sitters, Gerrit; Candelli, Andrea Nature, Vol. 535, Issue 7613 https://doi.org/10.1038/nature18643	journal	July 2016
Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway Xing, Mengtan; Yang, Mingrui; Huo, Wei Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms7233	journal	February 2015
The nucleoskeleton protein IFFO1 immobilizes broken DNA and suppresses chromosome translocation during tumorigenesis Li, Wen; Bai, Xiuzhen; Li, Jun Nature Cell Biology, Vol. 21, Issue 10 https://doi.org/10.1038/s41556-019-0388-0	journal	September 2019
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
XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining Nemoz, Clement; Ropars, Virginie; Frit, Philippe Nature Structural & Molecular Biology, Vol. 25, Issue 10 https://doi.org/10.1038/s41594-018-0133-6	journal	October 2018
Structural mechanism of DNA-end synapsis in the non-homologous end joining pathway for repairing double-strand breaks: bridge over troubled ends Wu, Qian Biochemical Society Transactions, Vol. 47, Issue 6 https://doi.org/10.1042/bst20180518	journal	December 2019
Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes Pratt, A. J.; Shin, D. S.; Merz, G. E. Proceedings of the National Academy of Sciences, Vol. 111, Issue 43 https://doi.org/10.1073/pnas.1308531111	journal	October 2014
Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes Hung, Putzer J.; Chen, Bo-Ruei; George, Rosmy Cell Cycle, Vol. 16, Issue 3 https://doi.org/10.1080/15384101.2016.1253640	journal	January 2017
XLF and H2AX function in series to promote replication fork stability Chen, Bo-Ruei; Quinet, Annabel; Byrum, Andrea K. Journal of Cell Biology, Vol. 218, Issue 7 https://doi.org/10.1083/jcb.201808134	journal	May 2019
Structural and functional characterization of the PNKP–XRCC4–LigIV DNA repair complex Aceytuno, R. Daniel; Piett, Cortt G.; Havali-Shahriari, Zahra Nucleic Acids Research, Vol. 45, Issue 10 https://doi.org/10.1093/nar/gkx275	journal	April 2017
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
Cernunnos Deficiency Reduces Thymocyte Life Span and Alters the T Cell Repertoire in Mice and Humans Vera, G.; Rivera-Munoz, P.; Abramowski, V. Molecular and Cellular Biology, Vol. 33, Issue 4 https://doi.org/10.1128/mcb.01057-12	journal	December 2012
XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair Mahaney, Brandi L.; Hammel, Michal; Meek, Katheryn Biochemistry and Cell Biology, Vol. 91, Issue 1 https://doi.org/10.1139/bcb-2012-0058	journal	February 2013
Consider the workhorse: Nonhomologous end-joining in budding yeast Emerson, Charlene H.; Bertuch, Alison A. Biochemistry and Cell Biology, Vol. 94, Issue 5 https://doi.org/10.1139/bcb-2016-0001	journal	October 2016
Transposon Invasion of the Paramecium Germline Genome Countered by a Domesticated PiggyBac Transposase and the NHEJ Pathway Dubois, Emeline; Bischerour, Julien; Marmignon, Antoine International Journal of Evolutionary Biology, Vol. 2012 https://doi.org/10.1155/2012/436196	journal	July 2012
Dissection of DNA double-strand-break repair using novel single-molecule forceps. Wang, Jing L.; Duboc, Camille; Wu, Qian Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.62968	text	January 2018
Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes Hung, Putzer J.; Chen, Bo-Ruei; George, Rosmy Taylor & Francis https://doi.org/10.6084/m9.figshare.4220484	audiovisual	January 2017
Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-homologous end joining in lymphocytes Hung, Putzer J.; Chen, Bo-Ruei; George, Rosmy Taylor & Francis https://doi.org/10.6084/m9.figshare.4220484.v2	audiovisual	January 2017

Similar Records

Crystal Structure of Human XLF: A Twist in Nonhomologous DNA End-Joining

Journal Article · Sun Dec 31 23:00:00 EST 2006 · Molecular Cell · OSTI ID:959938

Structural and Functional Interaction Between the Human DNA Repair Proteins DNA ligase IV and XRCC4

Journal Article · Wed Dec 31 23:00:00 EST 2008 · Molecular and Cellular Biology · OSTI ID:980493

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology

XRCC4 Protein Interactions with XRCC4-like Factor (XLF) Create an Extended Grooved Scaffold for DNA Ligation and Double Strand Break Repair

Citation Formats

References (61)

Cited By (51)

Similar Records

Related Subjects