Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus

Rashid, Ishtiaque; Hammel, Michal; Sverzhinsky, Aleksandr; Tsai, Miaw-Sheue; Pascal, John M.; Tainer, John A.; Tomkinson, Alan E.

doi:10.1016/j.jbc.2021.100921

Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus

Journal Article · Fri Jun 25 00:00:00 EDT 2021 · Journal of Biological Chemistry

DOI:https://doi.org/10.1016/j.jbc.2021.100921· OSTI ID:1825697

Rashid, Ishtiaque ^[1]; ^[2]; ^[3]; ^[2]; ^[3]; ^[4]; ^[1]

Univ. of New Mexico, Albuquerque, NM (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of Montreal, QC (Canada)
Univ. of Houston, TX (United States)

Tyrosyl DNA phosphodiesterase 1 (TDP1) and DNA Ligase IIIα (LigIIIα) are key enzymes in single-strand break (SSB) repair. TDP1 removes 3'-tyrosine residues remaining after degradation of DNA topoisomerase (TOP) 1 cleavage complexes trapped by either DNA lesions or TOP1 inhibitors. It is not known how TDP1 is linked to subsequent processing and LigIIIα-catalyzed joining of the SSB. Here we define a direct interaction between the TDP1 catalytic domain and the LigIII DNA-binding domain (DBD) regulated by conformational changes in the unstructured TDP1 N-terminal region induced by phosphorylation and/or alterations in amino acid sequence. Full-length and N-terminally truncated TDP1 are more effective at correcting SSB repair defects in TDP1 null cells compared with full-length TDP1 with amino acid substitutions of an N-terminal serine residue phosphorylated in response to DNA damage. TDP1 forms a stable complex with LigIII_170-755, as well as full-length LigIIIα alone or in complex with the DNA repair scaffold protein XRCC1. Small-angle X-ray scattering and negative stain electron microscopy combined with mapping of the interacting regions identified a TDP1/LigIIIα compact dimer of heterodimers in which the two LigIII catalytic cores are positioned in the center, whereas the two TDP1 molecules are located at the edges of the core complex flanked by highly flexible regions that can interact with other repair proteins and SSBs. As TDP1and LigIIIα together repair adducts caused by TOP1 cancer chemotherapy inhibitors, the defined interaction architecture and regulation of this enzyme complex provide insights into a key repair pathway in nonmalignant and cancer cells.

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)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1825697

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 2 Vol. 297; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (82)

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
Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. Kubota, Y.; Nash, R. A.; Klungland, A. The EMBO Journal, Vol. 15, Issue 23 https://doi.org/10.1002/j.1460-2075.1996.tb01056.x	journal	December 1996
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Mechanisms and Consequences of Double-Strand DNA Break Formation in Chromatin: DOUBLE-STRAND DNA BREAK FORMATION IN CHROMATIN Cannan, Wendy J.; Pederson, David S. Journal of Cellular Physiology, Vol. 231, Issue 1 https://doi.org/10.1002/jcp.25048	journal	September 2015
X‐ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double‐strand break repair impacting cell and cancer biology Hammel, Michal; Tainer, John A. Protein Science, Vol. 30, Issue 9 https://doi.org/10.1002/pro.4133	journal	June 2021
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
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
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
XRCC1 Stimulates Human Polynucleotide Kinase Activity at Damaged DNA Termini and Accelerates DNA Single-Strand Break Repair Whitehouse, Claire J.; Taylor, Richard M.; Thistlethwaite, Angela Cell, Vol. 104, Issue 1 https://doi.org/10.1016/S0092-8674(01)00195-7	journal	January 2001
Role of a BRCT domain in the interaction of DNA ligase III-α with the DNA repair protein XRCC1 Taylor, Richard M.; Wickstead, Bill; Cronin, Sam Current Biology, Vol. 8, Issue 15 https://doi.org/10.1016/S0960-9822(07)00350-8	journal	July 1998
The Crystal Structure of Human Tyrosyl-DNA Phosphodiesterase, Tdp1 Davies, Douglas R.; Interthal, Heidrun; Champoux, James J. Structure, Vol. 10, Issue 2 https://doi.org/10.1016/S0969-2126(02)00707-4	journal	February 2002
Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions Plo, I. DNA Repair, Vol. 2, Issue 10 https://doi.org/10.1016/S1568-7864(03)00116-2	journal	October 2003
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
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
Efficient Single-Strand Break Repair Requires Binding to Both Poly(ADP-Ribose) and DNA by the Central BRCT Domain of XRCC1 Polo, Luis M.; Xu, Yingqi; Hornyak, Peter Cell Reports, Vol. 26, Issue 3 https://doi.org/10.1016/j.celrep.2018.12.082	journal	January 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 comings and goings of PARP-1 in response to DNA damage Pascal, John M. DNA Repair, Vol. 71 https://doi.org/10.1016/j.dnarep.2018.08.022	journal	November 2018
Automated electron microscope tomography using robust prediction of specimen movements Mastronarde, David N. Journal of Structural Biology, Vol. 152, Issue 1 https://doi.org/10.1016/j.jsb.2005.07.007	journal	October 2005
A clustering approach to multireference alignment of single-particle projections in electron microscopy Sorzano, C. O. S.; Bilbao-Castro, J. R.; Shkolnisky, Y. Journal of Structural Biology, Vol. 171, Issue 2 https://doi.org/10.1016/j.jsb.2010.03.011	journal	August 2010
RELION: Implementation of a Bayesian approach to cryo-EM structure determination Scheres, Sjors H. W. Journal of Structural Biology, Vol. 180, Issue 3, p. 519-530 https://doi.org/10.1016/j.jsb.2012.09.006	journal	December 2012
Scipion: A software framework toward integration, reproducibility and validation in 3D electron microscopy de la Rosa-Trevín, J. M.; Quintana, A.; del Cano, L. Journal of Structural Biology, Vol. 195, Issue 1 https://doi.org/10.1016/j.jsb.2016.04.010	journal	July 2016
The Importance of Poly(ADP-Ribose) Polymerase as a Sensor of Unligated Okazaki Fragments during DNA Replication Hanzlikova, Hana; Kalasova, Ilona; Demin, Annie A. Molecular Cell, Vol. 71, Issue 2 https://doi.org/10.1016/j.molcel.2018.06.004	journal	July 2018
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
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
Biophysical Characterization of Human XRCC1 and Its Binding to Damaged and Undamaged DNA ^† Mani, Rajam S.; Karimi-Busheri, Feridoun; Fanta, Mesfin Biochemistry, Vol. 43, Issue 51 https://doi.org/10.1021/bi048615m	journal	December 2004
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
XRCC1 Protein Interacts with One of Two Distinct Forms of DNA Ligase III Nash, Rachel A.; Caldecott, Keith W.; Barnes, Deborah E. Biochemistry, Vol. 36, Issue 17 https://doi.org/10.1021/bi962281m	journal	April 1997
Drugging Topoisomerases: Lessons and Challenges Pommier, Yves ACS Chemical Biology, Vol. 8, Issue 1 https://doi.org/10.1021/cb300648v	journal	January 2013
Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK Das, Benu Brata; Antony, Smitha; Gupta, Shalu The EMBO Journal, Vol. 28, Issue 23 https://doi.org/10.1038/emboj.2009.302	journal	October 2009
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
Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1 El-Khamisy, Sherif F.; Saifi, Gulam M.; Weinfeld, Michael Nature, Vol. 434, Issue 7029 https://doi.org/10.1038/nature03314	journal	March 2005
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
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy Farmer, Hannah; McCabe, Nuala; Lord, Christopher J. Nature, Vol. 434, Issue 7035 https://doi.org/10.1038/nature03445	journal	April 2005
The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates Ahel, Ivan; Rass, Ulrich; El-Khamisy, Sherif F. Nature, Vol. 443, Issue 7112 https://doi.org/10.1038/nature05164	journal	September 2006
A human 5′-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage Ledesma, Felipe Cortes; El Khamisy, Sherif F.; Zuma, Maria C. Nature, Vol. 461, Issue 7264 https://doi.org/10.1038/nature08444	journal	October 2009
DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair Gao, Yankun; Katyal, Sachin; Lee, Youngsoo Nature, Vol. 471, Issue 7337 https://doi.org/10.1038/nature09773	journal	March 2011
Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair Simsek, Deniz; Furda, Amy; Gao, Yankun Nature, Vol. 471, Issue 7337 https://doi.org/10.1038/nature09794	journal	March 2011
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
XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia Hoch, Nicolas C.; Hanzlikova, Hana; Rulten, Stuart L. Nature, Vol. 541, Issue 7635 https://doi.org/10.1038/nature20790	journal	December 2016
Mutations in PNKP cause microcephaly, seizures and defects in DNA repair Shen, Jun; Gilmore, Edward C.; Marshall, Christine A. Nature Genetics, Vol. 42, Issue 3 https://doi.org/10.1038/ng.526	journal	January 2010
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin Moreira, Maria-Céu; Barbot, Clara; Tachi, Nobutada Nature Genetics, Vol. 29, Issue 2 https://doi.org/10.1038/ng1001-189	journal	October 2001
Mutation of TDP1, encoding a topoisomerase I–dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy Takashima, Hiroshi; Boerkoel, Cornelius F.; John, Joy Nature Genetics, Vol. 32, Issue 2 https://doi.org/10.1038/ng987	journal	September 2002
Prevention of overfitting in cryo-EM structure determination Scheres, Sjors H. W.; Chen, Shaoxia Nature Methods, Vol. 9, Issue 9 https://doi.org/10.1038/nmeth.2115	journal	July 2012
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination Punjani, Ali; Rubinstein, John L.; Fleet, David J. Nature Methods, Vol. 14, Issue 3 https://doi.org/10.1038/nmeth.4169	journal	February 2017
Topoisomerase I inhibitors: camptothecins and beyond Pommier, Yves Nature Reviews Cancer, Vol. 6, Issue 10 https://doi.org/10.1038/nrc1977	journal	October 2006
Single-strand break repair and genetic disease Caldecott, Keith W. Nature Reviews Genetics, Vol. 9, Issue 8 https://doi.org/10.1038/nrg2380	journal	August 2008
Structural basis for recognition of 5′-phosphotyrosine adducts by Tdp2 Shi, Ke; Kurahashi, Kayo; Gao, Rui Nature Structural & Molecular Biology, Vol. 19, Issue 12 https://doi.org/10.1038/nsmb.2423	journal	October 2012
Structural basis for DNA 3′-end processing by human tyrosyl-DNA phosphodiesterase 1 Flett, Fiona J.; Ruksenaite, Emilija; Armstrong, Lee A. Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-017-02530-z	journal	January 2018
Double‐strand breaks arising by replication through a nick are repaired by cohesin‐dependent sister‐chromatid exchange Cortés‐Ledesma, Felipe; Aguilera, Andrés EMBO reports, Vol. 7, Issue 9 https://doi.org/10.1038/sj.embor.7400774	journal	August 2006
Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria Das, B. B.; Dexheimer, T. S.; Maddali, K. Proceedings of the National Academy of Sciences, Vol. 107, Issue 46 https://doi.org/10.1073/pnas.1009814107	journal	November 2010
Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer Vilenchik, M. M.; Knudson, A. G. Proceedings of the National Academy of Sciences, Vol. 100, Issue 22 https://doi.org/10.1073/pnas.2135498100	journal	October 2003
Mitochondrial Localization of PARP-1 Requires Interaction with Mitofilin and Is Involved in the Maintenance of Mitochondrial DNA Integrity Rossi, Marianna N.; Carbone, Mariarosaria; Mostocotto, Cassandra Journal of Biological Chemistry, Vol. 284, Issue 46 https://doi.org/10.1074/jbc.M109.025882	journal	November 2009
Human Mre11/Human Rad50/Nbs1 and DNA Ligase IIIα/XRCC1 Protein Complexes Act Together in an Alternative Nonhomologous End Joining Pathway Della-Maria, Julie; Zhou, Yi; Tsai, Miaw-Sheue Journal of Biological Chemistry, Vol. 286, Issue 39 https://doi.org/10.1074/jbc.M111.274159	journal	August 2011
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
Human Tdp1 Cleaves a Broad Spectrum of Substrates, Including Phosphoamide Linkages Interthal, Heidrun; Chen, Hong Jing; Champoux, James J. Journal of Biological Chemistry, Vol. 280, Issue 43 https://doi.org/10.1074/jbc.M508898200	journal	August 2005
DNA ligaseI is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories Montecucco, A. The EMBO Journal, Vol. 17, Issue 13 https://doi.org/10.1093/emboj/17.13.3786	journal	July 1998
XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions Vidal, A. E. The EMBO Journal, Vol. 20, Issue 22 https://doi.org/10.1093/emboj/20.22.6530	journal	November 2001
Characterization of the XRCC1-DNA ligase III complex in vitro and its absence from mutant hamster cells Caldecott, Keith W.; Tucker, James D.; Stanker, Lawrence H. Nucleic Acids Research, Vol. 23, Issue 23 https://doi.org/10.1093/nar/23.23.4836	journal	January 1995
XRCC1 Polypeptide Interacts with DNA Polymerase and Possibly Poly (ADP-Ribose) Polymerase, and DNA Ligase III Is a Novel Molecular 'Nick-Sensor' In Vitro Caldecott, K. W.; Aoufouchi, S.; Johnson, P. Nucleic Acids Research, Vol. 24, Issue 22 https://doi.org/10.1093/nar/24.22.4387	journal	November 1996
Mitochondrial DNA ligase III function is independent of Xrcc1 Lakshmipathy, U. Nucleic Acids Research, Vol. 28, Issue 20 https://doi.org/10.1093/nar/28.20.3880	journal	October 2000
An atypical BRCT–BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex Hammel, Michal; Rashid, Ishtiaque; Sverzhinsky, Aleksandr Nucleic Acids Research, Vol. 49, Issue 1 https://doi.org/10.1093/nar/gkaa1188	journal	December 2020
Translocation of XRCC1 and DNA ligase III from centrosomes to chromosomes in response to DNA damage in mitotic human cells Okano, S. Nucleic Acids Research, Vol. 33, Issue 1 https://doi.org/10.1093/nar/gki190	journal	January 2005
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
The structural basis for partitioning of the XRCC1/DNA ligase III-α BRCT-mediated dimer complexes Cuneo, Matthew J.; Gabel, Scott A.; Krahn, Joseph M. Nucleic Acids Research, Vol. 39, Issue 17 https://doi.org/10.1093/nar/gkr419	journal	June 2011
TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs Huang, S. -y. N.; Murai, J.; Dalla Rosa, I. Nucleic Acids Research, Vol. 41, Issue 16 https://doi.org/10.1093/nar/gkt483	journal	June 2013
PARP1–TDP1 coupling for the repair of topoisomerase I–induced DNA damage Das, Benu Brata; Huang, Shar-yin N.; Murai, Junko Nucleic Acids Research, Vol. 42, Issue 7 https://doi.org/10.1093/nar/gku088	journal	January 2014
Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function Szczesny, Bartosz; Brunyanszki, Attila; Olah, Gabor Nucleic Acids Research, Vol. 42, Issue 21 https://doi.org/10.1093/nar/gku1089	journal	November 2014
The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function Breslin, Claire; Hornyak, Peter; Ridley, Andrew Nucleic Acids Research, Vol. 43, Issue 14 https://doi.org/10.1093/nar/gkv623	journal	June 2015
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
XRCC1 promotes replication restart, nascent fork degradation and mutagenic DNA repair in BRCA2-deficient cells Eckelmann, Bradley J.; Bacolla, Albino; Wang, Haibo NAR Cancer, Vol. 2, Issue 3 https://doi.org/10.1093/narcan/zcaa013	journal	August 2020
The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response Li, M.; Lu, L. -Y.; Yang, C. -Y. Genes & Development, Vol. 27, Issue 16 https://doi.org/10.1101/gad.226357.113	journal	August 2013
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
An alternative splicing event which occurs in mouse pachytene spermatocytes generates a form of DNA ligase III with distinct biochemical properties that may function in meiotic recombination. Mackey, Z. B.; Ramos, W.; Levin, D. S. Molecular and Cellular Biology, Vol. 17, Issue 2 https://doi.org/10.1128/MCB.17.2.989	journal	February 1997
The Human DNA Ligase III Gene Encodes Nuclear and Mitochondrial Proteins Lakshmipathy, Uma; Campbell, Colin Molecular and Cellular Biology, Vol. 19, Issue 5 https://doi.org/10.1128/MCB.19.5.3869	journal	May 1999
Spatial and Temporal Cellular Responses to Single-Strand Breaks in Human Cells Okano, Satoshi; Lan, Li; Caldecott, Keith W. Molecular and Cellular Biology, Vol. 23, Issue 11 https://doi.org/10.1128/MCB.23.11.3974-3981.2003	journal	June 2003
The Mechanism of Double-Strand DNA Break Repair by the Nonhomologous DNA End-Joining Pathway Lieber, Michael R. Annual Review of Biochemistry, Vol. 79, Issue 1 https://doi.org/10.1146/annurev.biochem.052308.093131	journal	June 2010
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
SUMO-Targeted Ubiquitin Ligase, Rad60, and Nse2 SUMO Ligase Suppress Spontaneous Top1–Mediated DNA Damage and Genome Instability Heideker, Johanna; Prudden, John; Perry, J. Jefferson P. PLoS Genetics, Vol. 7, Issue 3 https://doi.org/10.1371/journal.pgen.1001320	journal	March 2011
The Role of DNA Single- and Double-Strand Breaks in Cell Killing by Ionizing Radiation Olive, Peggy L. Radiation Research, Vol. 150, Issue 5 https://doi.org/10.2307/3579807	journal	November 1998
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
TDP1 serine 81 promotes interaction with DNA ligase IIIα and facilitates cell survival following DNA damage Chiang, Shih-Chieh; Carroll, Jean; El-Khamisy, Sherif F. Cell Cycle, Vol. 9, Issue 3 https://doi.org/10.4161/cc.9.3.10598	journal	February 2010
Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2 Kimanius, Dari; Forsberg, Björn O.; Scheres, Sjors HW eLife, Vol. 5 https://doi.org/10.7554/eLife.18722	journal	November 2016

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Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus

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