Amyotrophic lateral sclerosis-associated TDP-43 mutation Q331K prevents nuclear translocation of XRCC4-DNA ligase 4 complex and is linked to genome damage-mediated neuronal apoptosis
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Dominant mutations in the RNA/DNA-binding protein TDP-43 have been linked to amyotrophic lateral sclerosis (ALS). Here, we screened genomic DNA extracted from spinal cord specimens of sporadic ALS patients for mutations in the TARDBP gene and identified a patient specimen with previously reported Q331K mutation. The patient spinal cord tissue with Q331K mutation showed accumulation of higher levels of DNA strand breaks and the DNA double-strand break (DSB) marker γH2AX, compared to age-matched controls, suggesting a role of the Q331K mutation in genome-damage accumulation. Using conditional SH-SY5Y lines ectopically expressing wild-type (WT) or Q331K-mutant TDP-43, we confirmed the increased cytosolic sequestration of the poly-ubiquitinated and aggregated form of mutant TDP-43, which correlated with increased genomic DNA strand breaks, activation of the DNA damage response factors phospho-ataxia-telangiectasia mutated (ATM), phospho-53BP1, γH2AX and neuronal apoptosis. We recently reported the involvement of WT TDP-43 in non-homologous end joining (NHEJ)-mediated DSB repair, where it acts as a scaffold for the recruitment of XRCC4-DNA ligase 4 complex. Here, the mutant TDP-43, due to its reduced interaction and enhanced cytosolic mislocalization, prevented the nuclear translocation of XRCC4-DNA ligase 4. Consistently, the mutant cells showed significantly reduced DNA strand break sealing activity and were sensitized to DNA-damaging drugs. In addition, the mutant cells showed elevated levels of reactive oxygen species, suggesting both dominant negative and loss-of-function effects of the mutation. Together, our study uncovered an association of sporadic Q331K mutation with persistent genome damage accumulation due to both damage induction and repair defects.
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TDP-43 is directly involved in NHEJ through its recruitment and stabilization of the XRCC4-LIG4 complex at DSBs.
“Recently, TDP‐43 was also found to be directly involved in NHEJ through its recruitment and stabilization of the XRCC4‐LIG4 complex at DSBs (Guerrero et al, 2019; Mitra et al, 2019).”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Guerrero et al, 2019
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1 retracted
TDP-43 causes neurotoxicity and cytoskeletal dysfunction in primary cortical neurons
Baskaran, P., Shaw, C. E., & Guthrie, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196528 · Cited by 30 · see citing works
RetractedUbiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576 · see citing works
The Comet Assay for DNA Damage and Repair: Principles, Applications, and Limitations
Collins, A. R. (2004) · Molecular Biotechnology · doi:10.1385/mb:26:3:249 · Cited by 2,892 · see citing works
Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.093 · Cited by 2,732 · see citing works
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630 · see citing works
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis
Kabashi, E., Valdmanis, P. N., Dion, P., Spiegelman, D., McConkey, B. J., Velde, C. V., Bouchard, J.-P., Lacomblez, L., Pochigaeva, K., Salachas, F., et al. (2008) · Nature Genetics · doi:10.1038/ng.132 · Cited by 1,544 · see citing works
Oxidative Stress in Neurodegenerative Diseases
Simonian, N. A., & Coyle, J. T. (1996) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.36.040196.000503 · Cited by 1,377 · see citing works
Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357 · see citing works
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., Ling, S.-C., Sun, E., Wancewicz, E., Mazur, C., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2779 · Cited by 1,335 · see citing works
Characterizing the RNA targets and position-dependent splicing regulation by TDP-43
Tollervey, J. R., Curk, T., Rogelj, B., Briese, M., Cereda, M., Kayikci, M., König, J., Hortobágyi, T., Nishimura, A. L., Župunski, V., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2778 · Cited by 1,165 · see citing works
TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Amador‐Ortiz, C., Lin, W., Ahmed, Z., Personett, D., Davies, P., Duara, R., Graff‐Radford, N. R., Hutton, M. L., & Dickson, D. W. (2007) · Annals of Neurology · doi:10.1002/ana.21154 · Cited by 916 · see citing works
Johnson, B. S., Snead, D., Lee, J. J., McCaffery, J. M., Shorter, J., & Gitler, A. D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.010264 · Cited by 790 · see citing works
Van Deerlin, V. M., Leverenz, J. B., Bekris, L. M., Bird, T. D., Yuan, W., Elman, L. B., Clay, D., Wood, E. M., Chen-Plotkin, A. S., Martinez-Lage, M., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70071-1 · Cited by 723 · see citing works
Winton, M. J., Igaz, L. M., Wong, M. M., Kwong, L. K., Trojanowski, J. Q., & Lee, V. M. ‐. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800342200 · Cited by 660 · see citing works
TDP‐43 A315T mutation in familial motor neuron disease
Gitcho, M. A., Baloh, R. H., Chakraverty, S., Mayo, K., Norton, J. B., Levitch, D., Hatanpaa, K. J., White, C. L., Bigio, E. H., Caselli, R. J., et al. (2008) · Annals of Neurology · doi:10.1002/ana.21344 · Cited by 619 · see citing works
TDP‐43 regulates its mRNA levels through a negative feedback loop
Ayala, Y. M., Conti, L. D., Avendaño-Vázquez, S. E., Dhir, A., Romano, M., D’Ambrogio, A., Tollervey, J. R., Ule, J., Baralle, M., Buratti, E., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.310 · Cited by 618 · see citing works
Oxidative stress in neurodegenerative diseases.
Chen, X., Guo, C., & Kong, J. (2012) · Europe PMC (PubMed Central) · doi:10.3969/j.issn.1673-5374.2012.05.009 · Cited by 572 · see citing works
Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., Arnold, S. E., Siderowf, A., Grossman, M., Leverenz, J. B., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0261-2 · Cited by 468 · see citing works
The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity
Wang, W., Wang, L., Lu, J., Siedlak, S. L., Fujioka, H., Liang, J., Jiang, S., Ma, X., Jiang, Z., da Rocha, E. L., et al. (2016) · Nature Medicine · doi:10.1038/nm.4130 · Cited by 453 · see citing works
TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes
Kawahara, Y., & Mieda-Sato, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112427109 · Cited by 449 · see citing works
Oxidative Stress in Neurodegenerative Diseases
Crichton, R. R., & Ward, R. J. (2013) · Wiley eBooks · doi:10.1002/9781118553480.ch04 · Cited by 372 · see citing works
DNA damage-induced reactive oxygen species (ROS) stress response in Saccharomyces cerevisiae
Rowe, L. A., Degtyareva, N. P., & Doetsch, P. W. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.07.018 · Cited by 331 · see citing works
Igaz, L. M., Kwong, L. K., Xu, Y., Truax, A. C., Uryu, K., Neumann, M., Clark, C. M., Elman, L. B., Miller, B. L., Grossman, M., et al. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080003 · Cited by 328 · see citing works
Mitra, J., Guerrero, E. N., Hegde, P. M., Liachko, N. F., Wang, H., Vasquez, V., Gao, J., Pandey, A., Taylor, J. P., Kraemer, B. C., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818415116 · Cited by 305 · see citing works
Self-citationDavidson, Y. S., Kelley, T., Mackenzie, I. R., Pickering-Brown, S. M., du Plessis, D., Neary, D., Snowden, J. S., & Mann, D. M. A. (2007) · Acta Neuropathologica · doi:10.1007/s00401-006-0189-y · Cited by 299 · see citing works
Butterfield, D. A., Lange, M. L. B., & Rukhsana Sultana, A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.02.005 · Cited by 298 · see citing works
The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation
Buratti, E., & Baralle, F. E. (2010) · RNA Biology · doi:10.4161/rna.7.4.12205 · Cited by 284 · see citing works
Crystal structure of an Xrcc4-DNA ligase IV complex.
Sibanda, B. L., Critchlow, S. E., Begun, J., Pei, X. Y., Jackson, S. P., Blundell, T. L., & Pellegrini, L. (2001) · Nature Structural Biology · doi:10.1038/nsb725 · Cited by 256 · see citing works
Larasati, Y. A., Yoneda‐Kato, N., Nakamae, I., Yokoyama, T., Meiyanto, E., & Kato, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-20179-6 · Cited by 209 · see citing works
Wang, H., Guo, W., Mitra, J., Hegde, P. M., Vandoorne, T., Eckelmann, B. J., Mitra, S., Tomkinson, A. E., Van Den Bosch, L., & Hegde, M. L. (2018) · Nature Communications · doi:10.1038/s41467-018-06111-6 · Cited by 205 · see citing works
Lim, L., Wei, Y., Lu, Y., & Song, J. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002338 · Cited by 199 · see citing works
TDP-43 interacts with mitochondrial proteins critical for mitophagy and mitochondrial dynamics
Davis, S. A., Itaman, S., Janney, C., Sherard, J. A., Dowell, J. A., Cairns, N. J., & Gitcho, M. A. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.04.053 · Cited by 159 · see citing works
Chakraborty, A., Tapryal, N., Venkova, T., Horikoshi, N., PANDITA, R. K., Sarker, A. H., Sarkar, P. S., Pandita, T. K., & Hazra, T. K. (2016) · Nature Communications · doi:10.1038/ncomms13049 · Cited by 155 · see citing works
Interaction of the Human DNA Glycosylase NEIL1 with Proliferating Cell Nuclear Antigen
Hong, D., Theriot, C. A., Das, A., Hegde, M. L., Matsumoto, Y., Boldogh, I. R., Hazra, T. K., Bhakat, K. K., & MITRA, S. P. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m709186200 · Cited by 147 · see citing works
Self-citationTDP-43/FUS in motor neuron disease: Complexity and challenges
Guerrero, E. N., Wang, H., Mitra, J., Hegde, P. M., Stowell, S. E., Liachko, N. F., Kraemer, B. C., Garruto, R. M., Rao, K. S. J., & Hegde, M. L. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.09.004 · Cited by 144 · see citing works
Self-citationTDP-43 in differential diagnosis of motor neuron disorders
Dickson, D. W., Josephs, K. A., & Amador, C. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0234-5 · Cited by 143 · see citing works
Leverenz, J. B., Yu, C. E., Montine, T. J., Steinbart, E., Bekris, L. M., Zabetian, C., Kwong, L. K., Lee, V. M.-Y., Schellenberg, G. D., & Bird, T. D. (2007) · Brain · doi:10.1093/brain/awm069 · Cited by 129 · see citing works
Mitchell, J. C., Constable, R., So, E., Vance, C. A., Scotter, E. L., Glover, L., Hortobágyi, T., Arnold, E. S., Ling, S., McAlonis‐Downes, M., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0212-4 · Cited by 118 · see citing works
Hegde, M. L., Hegde, P. M., Bellot, L. J., Mandal, S. M., Hazra, T. K., Li, G., Boldogh, I. R., Tomkinson, A. E., & MITRA, S. P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304231110 · Cited by 105 · see citing works
Self-citationInduction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus
Martínez, I., García-Carpizo, V., Guijarro, T., García-Gomez, A., Navarro, D., Aranda, A., & Zambrano, A. (2016) · Virulence · doi:10.1080/21505594.2016.1144001 · Cited by 68 · see citing works
Analysis of Oxidative Damage by Gene‐Specific Quantitative PCR
Kovalenko, O. A., & Santos, J. H. (2009) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg1901s62 · Cited by 49 · see citing works
NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells
Sarker, A. H., Chatterjee, A., Williams, M., Lin, S., Havel, C., Jacob III, P., Boldogh, I., Hazra, T. K., Talbot, P., & Hang, B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090261 · Cited by 44 · see citing works
DNA Ligase IV regulates XRCC4 nuclear localization
Francis, D. B., Kozlov, M., Chavez, J., Chu, J., Malu, S., Hanna, M., & Cortés, P. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.05.010 · Cited by 27 · see citing works
Oxidative DNA Damage in Neurons: Implication of Ku in Neuronal Homeostasis and Survival
Zio, D. D., Bordi, M., & Cecconi, F. (2012) · International Journal of Cell Biology · doi:10.1155/2012/752420 · Cited by 25 · see citing works
An Inducible Alpha-Synuclein Expressing Neuronal Cell Line Model for Parkinson’s Disease1
Vasquez, V., Mitra, J., Perry, G. L., Rao, K. S. J., & Hegde, M. L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180610 · Cited by 17 · see citing works
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The role of TDP-43 mislocalization in amyotrophic lateral sclerosis
Suk, T. R., & Rousseaux, M. W. C. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00397-1 · Cited by 456 · see citing works
Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations
Konopka, A., Whelan, D. R., Jamali, M. S., Perri, E. R., Shahheydari, H., Toth, R. P., Parakh, S., Robinson, T., Cheong, A., Mehta, P. M., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00386-4 · Cited by 109 · see citing works
Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD
Wood, A., Gurfinkel, Y., Polain, N., Lamont, W. G., & Rea, S. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094705 · Cited by 101 · see citing works
Giannini, M., Bayona‐Feliú, A., Sproviero, D., Barroso, S. I., Cereda, C., & Aguilera, A. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1009260 · Cited by 96 · see citing works
Nonhomologous end joining: new accessory factors fine tune the machinery
Ghosh, D., & Raghavan, S. C. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.03.001 · Cited by 83 · see citing works
DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity
Kok, J. R., Palminha, N. M., Souza, C. D. S., El-Khamisy, S. F., & Ferraiuolo, L. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03872-0 · Cited by 83 · see citing works
TDP-43 pathology: From noxious assembly to therapeutic removal
Keating, S. S., Gil, R. S., Swanson, M. E. V., Scotter, E. L., & Walker, A. K. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102229 · Cited by 74 · see citing works
Boas, S. M., Joyce, K. L., & Cowell, R. M. (2021) · Antioxidants · doi:10.3390/antiox11010008 · Cited by 69 · see citing works
DNA Damage, Defective DNA Repair, and Neurodegeneration in Amyotrophic Lateral Sclerosis
Konopka, A., & Atkin, J. D. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.786420 · Cited by 66 · see citing works
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Tamaki, Y., Ross, J. P., Alipour, P., Castonguay, C.-E., Li, B., Catoire, H., Rochefort, D. L., Urushitani, M., Takahashi, R., Sonnen, J. A., et al. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010606 · Cited by 65 · see citing works
Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia
Marques, C., Held, A., Dorfman, K., Sung, J., Song, C., Kavuturu, A. S., Aguilar, C., Russo, T., Oakley, D. H., Albers, M. W., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02688-z · Cited by 65 · see citing works
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Pessina, F., Gioia, U., Brandi, O., Farina, S., Ceccon, M., Francia, S., & di Fagagna, F. D. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.09.006 · Cited by 58 · see citing works
Wang, H., Kodavati, M. M., Britz, G. W., & Hegde, M. L. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.784361 · Cited by 59 · see citing works
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Kawaguchi, T., Rollins, M. G., Moinpour, M., Morera, A. A., Ebmeier, C. C., Old, W. M., & Schwartz, J. C. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00575 · Cited by 50 · see citing works
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Petrozziello, T., Bordt, E. A., Mills, A. N., Kim, S. E., Sapp, E., Devlin, B. A., Obeng-Marnu, A. A., Farhan, S. M. K., Amaral, A. C. S., Dujardin, S., et al. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02557-w · Cited by 49 · see citing works
DNA double-strand breaks: a potential therapeutic target for neurodegenerative diseases
Thadathil, N., Hori, R. T., Xiao, J., & Khan, M. M. (2019) · Chromosome Research · doi:10.1007/s10577-019-09617-x · Cited by 48 · see citing works
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Romano, N., Catalani, A., Lattante, S., Belardo, A., Proietti, S., Bertini, L., Silvestri, F., Catalani, E., Cervia, D., Zolla, L., et al. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109591 · Cited by 28 · see citing works
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Mitra, J., Kodavati, M. M., Dharmalingam, P., Guerrero, E. N., Rao, K. S. J., Garruto, R. M., & Hegde, M. L. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-01962-9 · Cited by 19 · see citing works
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Gimenez, J., Spalloni, A., Cappelli, S., Ciaiola, F., Orlando, V., Buratti, E., & Longone, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813807 · Cited by 13 · see citing works
Kodavati, M. M., Rao, V. H. M., Provasek, V. E., & Hegde, M. L. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102413 · Cited by 14 · see citing works
Self-citationDashtmian, A. R., Darvishi, F. B., & Arnold, W. D. (2024) · Cells · doi:10.3390/cells13110928 · Cited by 12 · see citing works
Provasek, V. E., Bacolla, A., Rangaswamy, S., Kodavati, M. M., Mitra, J., Yusuf, I. O., Malojirao, V. H., Vasquez, V., Britz, G. W., Li, G., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf920 · Cited by 13 · see citing works
Self-citationHu, L., Mao, S., Li, L., Bai, G., Liu, B., & Mao, J. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105749 · Cited by 12 · see citing works
Dash, B. P., Freischmidt, A., Weishaupt, J. H., & Hermann, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179652 · Cited by 11 · see citing works
Wang, Y., Liu, L., Chen, H., Yang, Y., Mu, C., Ren, H., Liu, Y., Yu, L., Fang, Q., Wang, G., et al. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad163 · Cited by 10 · see citing works
Rafiee, M., Rohban, S., Davey, K., Ule, J., & Luscombe, N. M. (2023) · Brain · doi:10.1093/brain/awad046 · Cited by 9 · see citing works
The Molecular Intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS Pathogenesis
Watanabe, Y., Nakagawa, T., Nakagawa, M., & Nakayama, K. (2025) · Genes · doi:10.3390/genes16040407 · Cited by 8 · see citing works
Multiple ways to a dead end: diverse mechanisms by which ALS mutant genes induce cell death
Tsai, Y.-L., & Manley, J. L. (2021) · Cell Cycle · doi:10.1080/15384101.2021.1886661 · Cited by 8 · see citing works
Autologous treatment for ALS with implication for broad neuroprotection
Kim, D.-H., Kim, S., Sung, A., Patel, N., Wong, N., Conboy, M. J., & Conboy, I. M. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00290-5 · Cited by 7 · see citing works
Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?
Hall, B., George, J. G., & Allen, S. P. (2022) · PubMed · doi:10.14670/hh-18-404 · Cited by 6 · see citing works
Zhang, Y., Zeng, B., Gu, A., Kang, Q., Zhao, M., Peng, G., Zhou, M., Liu, W., Liu, M., Ding, L., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911333 · Cited by 6 · see citing works
Almalki, S., Salama, M. E., Taylor, M. J., Ahmed, Z., & Tuxworth, R. I. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1671906 · Cited by 5 · see citing works
Krupp, S., Hubbard, I., Tam, O. H., Hammell, M., & Dubnau, J. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010973 · Cited by 6 · see citing works
Ohene‐Nyako, M., Nass, S. R., Richard, H., Lukande, R. L., Nicol, M. R., McRae, M., Knapp, P. E., & Hauser, K. F. (2023) · ASN NEURO · doi:10.1177/17590914231158218 · Cited by 4 · see citing works
Folic acid prevents inner hair cell degeneration via genomic stability
Cai, R., Ma, X., Lu, J., Liu, H., Wang, M., Wang, Z., Xi, Q., Wu, H., Zhang, Z., & Liu, H. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02880-4 · Cited by 2 · see citing works
Mitra, J., Dharmalingam, P., Kodavati, M. M., Guerrero, E. N., Rao, K. S. J., Garruto, R. M., & Hegde, M. L. (2024) · Research Square · doi:10.21203/rs.3.rs-3879966/v2 · Cited by 2 · see citing works
Self-citationKrus, K. L., Benitez, A. M., Strickland, A. M., Milbrandt, J., Bloom, A. J., & DiAntonio, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.19.585052 · Cited by 2 · see citing works
TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stability
Moffatt, C., Arora, A., Vaeth, K. F., Guzmán, B. B., Bhardwaj, G., Hoelscher, A., Gifford, L. B., Russ, H. A., Dominguez, D., & Taliaferro, J. (2025) · EMBO Journal · doi:10.1038/s44318-025-00653-4 · Cited by 2 · see citing works
Chakraborty, A., Mitra, J., Malojirao, V. H., Kodavati, M. M., Mandal, S. M., Gill, S. K., Sreenivasmurthy, S. G., Vasquez, V., Mankevich, M., Bosch, L. V. D., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-09787-5 · Cited by 1 · see citing works
Self-citationThe Role of TDP-43 in Genome Repair and beyond in Amyotrophic Lateral Sclerosis
Mitra, J., & Hegde, M. L. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.92696 · Cited by 2 · see citing works
Self-citationShadfar, S., Vidal, M., Parakh, S., Laird, A. S., & Atkin, J. D. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.31.458441 · Cited by 1 · see citing works
Nonhomologous DNA End Joining in Mammalian Cells
Ray, U., & Raghavan, S. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00101-2 · Cited by 1 · see citing works
Mitra, J., Dharmalingam, P., Kodavati, M. M., Guerrero, E. N., Rao, K. S. J., & Hegde, M. L. (2024) · Research Square · doi:10.21203/rs.3.rs-3879966/v1 · Cited by 1 · see citing works
Self-citationGbadamosi, I., Binias, S., Gielniewski, B., Magno, R., Duarte, I., & Jawaid, A. (2025) · Scientific Data · doi:10.1038/s41597-025-05409-7
Xie, Y., Ke, Y., Wu, Y., Ding, C., Dickinson, S. E., Li, J., Jiang, Y., Zhao, S., Roh, E., Liu, K., et al. (2026) · Carcinogenesis · doi:10.1093/carcin/bgag014
Almalki, S., Salama, M. E., Taylor, M. J., Ahmed, Z., & Tuxworth, R. I. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1671909
TDP43 and hnRNP K Regulate Alternative Splicing of DNAJC5
Nagasse, H. Y., Okuda, E. K., & Coltri, P. P. (2026) · Cell Biology International · doi:10.1002/cbin.70158
Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
漆谷, 真., Tamaki, Y., & URUSHITANI, M. (n.d.) · Institutional Repositories DataBase (IRDB)
KIF4A stabilizes TDP43 to promote DNA damage repair and temozolomide resistance in glioblastoma
Guo, Q., Chen, W., Wen, L., Ji, Z., Ding, C., Ma, C., Huang, L., Shen, Y., & Zhu, Y. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118504
TDP-43 and ALS - what's wrong with my membranes?
Dahlhaus, R., Yalcin, I., Tischer, J., & Braun, R. J. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107630
- Authors
- Guerrero, E. N., Mitra, J., Wang, H., Rangaswamy, S., Hegde, P. M., Basu, P., Rao, K. S., & Hegde, M. L.
- Affiliations
- Houston Methodist (US)
- Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (PA)
- Corresponding author
- Hegde, Muralidhar L
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-04-01
- Volume
- 28
- Issue
- 15
- Pages
- 2459-2476
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC6867871
- OpenAlex
- W2933044054
- Cited by
- 68
- References
- 45
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 14 · 2021: 13 · 2020: 8 · 2019: 6
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01 NS088645)
- Muscular Dystrophy Association (MDA 294842)
- California Health Care Safety Net Institute
- Secretarí Nacional de Ciencia, Tecnologí e Innovación
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyotrophic lateral sclerosis, TDP-43, TARDBP, non-homologous end joining, DNA double-strand break repair, DNA damage response, neuronal apoptosis, γH2AX, ATM, 53BP1, reactive oxygen species, dominant negative mutation, DNA strand breaks, sporadic ALS
- MeSH terms
- DNA Ligase ATP, Amyotrophic Lateral Sclerosis, Cell Line, DNA, DNA Repair, DNA-Binding Proteins, Humans, Mutation, Neurons, Spinal Cord, Translocation, Genetic, RNA-Binding Proteins, Apoptosis, Polymorphism, Single Nucleotide, DNA Breaks, Double-Stranded
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