Profiling DNA break sites and transcriptional changes in response to contextual fear learning
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Abstract
Neuronal activity generates DNA double-strand breaks (DSBs) at specific loci in vitro and this facilitates the rapid transcriptional induction of early response genes (ERGs). Physiological neuronal activity, including exposure of mice to learning behaviors, also cause the formation of DSBs, yet the distribution of these breaks and their relation to brain function remains unclear. Here, following contextual fear conditioning (CFC) in mice, we profiled the locations of DSBs genome-wide in the medial prefrontal cortex and hippocampus using γH2AX ChIP-Seq. Remarkably, we found that DSB formation is widespread in the brain compared to cultured primary neurons and they are predominately involved in synaptic processes. We observed increased DNA breaks at genes induced by CFC in neuronal and non-neuronal nuclei. Activity-regulated and proteostasis-related transcription factors appear to govern some of these gene expression changes across cell types. Finally, we find that glia but not neurons have a robust transcriptional response to glucocorticoids, and many of these genes are sites of DSBs. Our results indicate that learning behaviors cause widespread DSB formation in the brain that are associated with experience-driven transcriptional changes across both neuronal and glial cells.
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DNA breaks serve a functional role in neuronal activity.
“DNA breaks seem to serve a functional role in neuronal activity”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Stott et al, 2021
Stimulating primary neurons with bicuculline or subjecting mice to fear learning results in the induction of DSBs at the promoters of immediate-early genes.
“Stimulating primary neurons with bicuculline or subjecting mice to fear learning results in the induction of DSBs at the promoters of immediate‐early genes”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Stott et al, 2021
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548 · see citing works
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259 · see citing works
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
HISAT: a fast spliced aligner with low memory requirements
Kim, D., Langmead, B., & Salzberg, S. L. (2015) · Nature Methods · doi:10.1038/nmeth.3317 · Cited by 24,112 · see citing works
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease
Cappello, V., Marchetti, L., Parlanti, P., Landi, S., Tonazzini, I., Cecchini, M., Piazza, V., & Gemmi, M. (2016) · Scientific Reports · doi:10.1038/s41598-016-0001-8 · Cited by 13,097 · see citing works
MEME SUITE: tools for motif discovery and searching
Bailey, T. L., Boden, M., Buske, F. A., Frith, M., Grant, C. E., Clementi, L., Ren, J., Li, W. W., & Noble, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp335 · Cited by 10,648 · see citing works
Double-slit photoelectron interference in strong-field ionization of the neon dimer
Kunitski, M., Eicke, N., Huber, P., Köhler, J., Zeller, S., Voigtsberger, J., Schlott, N., Henrichs, K., Sann, H., Trinter, F., et al. (2019) · Institutional Repository of Leibniz Universität Hannover (Leibniz Universität Hannover) · doi:10.15488/5174 · Cited by 8,378 · see citing works
Double-slit photoelectron interference in strong-field ionization of the neon dimer
Kunitski, M., Eicke, N., Huber, P., Köhler, J., Zeller, S., Voigtsberger, J., Schlott, N., Henrichs, K., Sann, H., Trinter, F., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-07882-8 · Cited by 8,162 · see citing works
In situ click chemistry generation of cyclooxygenase-2 inhibitors
Bhardwaj, A., Kaur, J., Wuest, M., & Wuest, F. (2017) · Nature Communications · doi:10.1038/s41467-016-0009-6 · Cited by 7,448 · see citing works
Molecular signatures database (MSigDB) 3.0
Liberzon, A., Subramanian, A., Pinchback, R., Thorvaldsdóttir, H., Tamayo, P., & Mesirov, J. P. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr260 · Cited by 7,111 · see citing works
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Walter, P., & Ron, D. (2011) · Science · doi:10.1126/science.1209038 · Cited by 5,893 · see citing works
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438 · see citing works
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502 · see citing works
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247 · see citing works
Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt
Durinck, S., Spellman, P. T., Birney, E., & Huber, W. K. (2009) · Nature Protocols · doi:10.1038/nprot.2009.97 · Cited by 4,081 · see citing works
Yoshida, H., Matsui, T., Yamamoto, A., Okada, T., & Mori, K. (2001) · Cell · doi:10.1016/s0092-8674(01)00611-0 · Cited by 4,054 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
deepTools: a flexible platform for exploring deep-sequencing data
Ramírez, F., Dündar, F., Diehl, S., Grüning, B. A., & Manke, T. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku365 · Cited by 3,738 · see citing works
Ranade, V. (2009) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e31817c941f · Cited by 2,790 · see citing works
Cellular Scaling Rules for the Brains of Marsupials: Not as “Primitive” as Expected
Santos, S. E. D., Porfírio, J., Cunha, F., Manger, P. R., Tavares, W. C., Pessôa, L. M., Raghanti, M. A., Sherwood, C. C., & Herculano‐Houzel, S. (2017) · Brain Behavior and Evolution · doi:10.1159/000452856 · Cited by 2,651 · see citing works
Single-cell transcriptomic analysis of Alzheimer’s disease
Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1195-2 · Cited by 2,568 · see citing works
Self-citationSMARCAD1 ATPase activity is required to silence endogenous retroviruses in embryonic stem cells
Sachs, P., Ding, D., Bergmaier, P., Lamp, B., Schlagheck, C., Finkernagel, F., Nist, A., Stiewe, T., & Mermoud, J. E. (2019) · Nature Communications · doi:10.1038/s41467-019-09078-0 · Cited by 2,388 · see citing works
NeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351 · see citing works
Rao, S. V., & Jollis, J. G. (2000) · Mayo Clinic Proceedings · doi:10.4065/75.10.991 · Cited by 2,230 · see citing works
Morimoto, R. I. (1998) · Genes & Development · doi:10.1101/gad.12.24.3788 · Cited by 1,898 · see citing works
Identifying ChIP-seq enrichment using MACS
Feng, J., Liu, T., Qin, B., Zhang, Y., & Liu, X. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.101 · Cited by 1,805 · see citing works
The environment and schizophrenia
van Os, J., Kenis, G., & Rutten, B. P. F. (2010) · Nature · doi:10.1038/nature09563 · Cited by 1,572 · see citing works
γH2AX: a sensitive molecular marker of DNA damage and repair
Mah, L.-J., El-Osta, A., & Karagiannis, T. C. (2010) · Leukemia · doi:10.1038/leu.2010.6 · Cited by 1,557 · see citing works
The contextual brain: implications for fear conditioning, extinction and psychopathology
Maren, S., Phan, K. L., & Liberzon, I. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3492 · Cited by 1,547 · see citing works
Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS
Nicolae, D. L., Gamazon, E., Zhang, W., Duan, S., Dolan, M. E., & Cox, N. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000888 · Cited by 1,292 · see citing works
DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis
Yu, G., Wang, L.-G., Yan, G., & He, Q. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu684 · Cited by 1,280 · see citing works
Yoshida, H., Haze, K., Yanagi, H., Yura, T., & Mori, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.50.33741 · Cited by 1,229 · see citing works
Mechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
Primary response genes induced by growth factors and tumor promoters.
Herschman, H. (1991) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.60.070191.001433 · Cited by 1,077 · see citing works
Massively parallel single-nucleus RNA-seq with DroNc-seq
Habib, N., Avraham-Davidi, I., Basu, A., Burks, T., Shekhar, K., Hofree, M., Choudhury, S. R., Aguet, F., Gelfand, E., Ardlie, K., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4407 · Cited by 1,069 · see citing works
Chromatin accessibility pre-determines glucocorticoid receptor binding patterns
John, S., Sabo, P. J., Thurman, R. E., Sung, M.-H., Biddie, S. C., Johnson, T. A., Hager, G. L., & Stamatoyannopoulos, J. A. (2011) · Nature Genetics · doi:10.1038/ng.759 · Cited by 954 · see citing works
Depression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944 · see citing works
Kulakovskiy, I. V., Vorontsov, I. E., Yevshin, I., Sharipov, R., Fedorova, A. D., Rumynskiy, E. I., Medvedeva, Y. A., Magana-Mora, A., Bajić, V. B., Papatsenko, D., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1106 · Cited by 921 · see citing works
The UCSC genome browser and associated tools
Kuhn, R. M., Haussler, D., & Kent, W. J. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs038 · Cited by 883 · see citing works
A Topoisomerase IIß-Mediated dsDNA Break Required for Regulated Transcription
Ju, B., Lunyak, V. V., Perissi, V., García-Bassets, I., Rose, D. W., Glass, C. K., & Rosenfeld, M. G. (2006) · Science · doi:10.1126/science.1127196 · Cited by 842 · see citing works
Love, M. I., Huber, W. K., & Anders, S. (2014) · Cited by 718 · see citing works
Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-Response Genes
Madabhushi, R., Gao, F., Pfenning, A. R., Pan, L., Yamakawa, S., Seo, J., Rueda, R., Phan, T. X., Yamakawa, H., Pao, P.-C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.032 · Cited by 700 · see citing works
Self-citationKreisel, T., Frank, M. G., Licht, T., Reshef, R., Ben-Menachem-Zidon, O., Baratta, M. V., Maier, S. F., & Yirmiya, R. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.155 · Cited by 663 · see citing works
DNA damage and its links to neurodegeneration
Madabhushi, R., Pan, L., & Tsai, L.-H. (2014) · Neuron · doi:10.1016/j.neuron.2014.06.034 · Cited by 654 · see citing works
Self-citationActivity-dependent regulation of inhibitory synapse development by Npas4
Lin, Y., Bloodgood, B. L., Hauser, J. L., Lapan, A. D., Koon, A. C., Kim, T.-K., Hu, L. S., Malik, A. N., & Greenberg, M. E. (2008) · Nature · doi:10.1038/nature07319 · Cited by 639 · see citing works
Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement
Adamsky, A., Kol, A., Kreisel, T., Doron, A., Ozeri-Engelhard, N., Melcer, T., Refaeli, R., Horn, H., Regev, L., Groysman, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.002 · Cited by 631 · see citing works
Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior
Yap, E.-L., & Greenberg, M. E. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.013 · Cited by 626 · see citing works
Psychiatric Adverse Effects of Corticosteroids
Warrington, T. P., & Bostwick, J. M. (2006) · Mayo Clinic Proceedings · doi:10.4065/81.10.1361 · Cited by 613 · see citing works
Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements
Haffner, M. C., Aryee, M. J., Toubaji, A., Esopi, D., Albadine, R., Gürel, B., Isaacs, W. B., Bova, G. S., Liu, W., Xu, J., et al. (2010) · Nature Genetics · doi:10.1038/ng.613 · Cited by 606 · see citing works
Lin, C., Yang, L., Tanasa, B., Hutt, K., Ju, B.-G., Ohgi, K. A., Zhang, J., Rose, D. W., Fu, X.-D., Glass, C. K., et al. (2009) · Cell · doi:10.1016/j.cell.2009.11.030 · Cited by 576 · see citing works
Enge, M., Arda, H. E., Mignardi, M., Beausang, J., Bottino, R., Kim, S. K., & Quake, S. R. (2017) · Cell · doi:10.1016/j.cell.2017.09.004 · Cited by 568 · see citing works
(2019) · Nature reviews. Neuroscience · doi:10.1038/41583.1471-0048 · Cited by 550 · see citing works
Tynan, R. J., Naicker, S., Hinwood, M., Nalivaiko, E., Buller, K. M., Pow, D. V., Day, T. A., & Walker, F. R. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.02.001 · Cited by 531 · see citing works
Sublime Microglia: Expanding Roles for the Guardians of the CNS
Salter, M. W., & Beggs, S. (2014) · Cell · doi:10.1016/j.cell.2014.06.008 · Cited by 531 · see citing works
Ten Surprising Facts About Stressful Life Events and Disease Risk
Cohen, S., Murphy, M. L. M., & Prather, A. A. (2019) · Annual Review of Psychology · doi:10.1146/annurev-psych-010418-102857 · Cited by 531 · see citing works
Mechanisms and Consequences of Double‐Strand DNA Break Formation in Chromatin
Cannan, W. J., & Pederson, D. S. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25048 · Cited by 499 · cited 1× · see citing works
“Additionally, two closely spaced single-strand DNA breaks (SSBs) could potentially be recognized as a DSB by the cell [71].”
BackgroundSingle-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex
Hrvatin, S., Hochbaum, D. R., Nagy, M. A., Cicconet, M., Robertson, K., Cheadle, L., Zilionis, R., Ratner, A., Borges-Monroy, R., Klein, A. M., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0029-5 · Cited by 497 · see citing works
Havis, E., & Duprez, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051664 · Cited by 497 · see citing works
Ludwig, L., Pasman, J. A., Nicholson, T., Aybek, S., David, A. S., Tuck, S., Kanaan, R. A., Roelofs, K., Carson, A., & Stone, J. (2018) · The Lancet Psychiatry · doi:10.1016/s2215-0366(18)30051-8 · Cited by 495 · see citing works
Suberbielle, E., Sanchez, P. E., Kravitz, A. V., Wang, X., Ho, K., Eilertson, K., Devidze, N., Kreitzer, A. C., & Mucke, L. (2013) · Nature Neuroscience · doi:10.1038/nn.3356 · Cited by 487 · see citing works
High Cortisol and the Risk of Dementia and Alzheimer’s Disease: A Review of the Literature
Ouanes, S., & Popp, J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00043 · Cited by 481 · see citing works
Czéh, B., Simon, M., Schmelting, B., Hiemke, C., & Fuchs, E. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300982 · Cited by 434 · see citing works
Mammalian heat shock response and mechanisms underlying its genome-wide transcriptional regulation
Mahat, D. B., Salamanca, H. H., Duarte, F. M., Danko, C. G., & Lis, J. T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.025 · Cited by 426 · see citing works
Is Non-Homologous End-Joining Really an Inherently Error-Prone Process?
Bétermier, M., Bertrand, P., & López, B. S. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004086 · Cited by 420 · see citing works
Hinwood, M., Morandini, J., Day, T. A., & Walker, F. R. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr229 · Cited by 420 · see citing works
Journal of Cellular Physiology
(2006) · Journal of Cellular Physiology · doi:10.1002/(issn)1097-4652 · Cited by 407 · see citing works
Immune cell regulation of glia during CNS injury and disease
Greenhalgh, A. D., David, S., & Bennett, F. C. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0263-9 · Cited by 398 · see citing works
Gene ontology semantic similarity analysis using GOSemSim
Yu, G. (2020) · Methods in Molecular Biology · doi:10.1007/978-1-0716-0301-7_11 · Cited by 392 · see citing works
Turinetto, V., & Giachino, C. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv061 · Cited by 373 · see citing works
BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks
Yan, W. X., Mirzazadeh, R., Garnerone, S., Scott, D., Schneider, M. W., Kallas, T., Custodio, J., Wernersson, E., Li, Y., Gao, L., et al. (2017) · Nature Communications · doi:10.1038/ncomms15058 · Cited by 369 · see citing works
Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance.
Liston, C., Cichon, J. M., Jeanneteau, F., Jia, Z., Chao, M. V., & Gan, W.-B. (2013) · Nature Neuroscience · doi:10.1038/nn.3387 · Cited by 358 · see citing works
DNA methylation changes in plasticity genes accompany the formation and maintenance of memory
Halder, R., Hennion, M., Vidal, R. O., Shomroni, O., Rahman, R.-U., Rajput, A., Centeno, T. P., van Bebber, F., Capece, V., Vizcaino, J. C. G., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4194 · Cited by 358 · see citing works
Bisht, K., Sharma, K. P., & Tremblay, M. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.05.003 · Cited by 351 · see citing works
Bozon, B., Davis, S., & Laroche, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00674-3 · Cited by 317 · see citing works
Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses
Frank, M. G., Thompson, B. M., Watkins, L. R., & Maier, S. F. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.10.005 · Cited by 310 · see citing works
Neuronal activity rapidly induces transcription of the CREB‐regulated microRNA‐132, in vivo
Nudelman, A. S., DiRocco, D. P., Lambert, T. J., Garelick, M. G., Le, J. H., Nathanson, N. M., & Storm, D. R. (2009) · Hippocampus · doi:10.1002/hipo.20646 · Cited by 300 · see citing works
Clouaire, T., Rocher, V., Lashgari, A., Arnould, C., Aguirrebengoa, M., Biernacka, A., Skrzypczak, M., Aymard, F., Fongang, B., Dojer, N., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.020 · Cited by 300 · see citing works
Npas4 Regulates a Transcriptional Program in CA3 Required for Contextual Memory Formation
Ramamoorthi, K., Fropf, R., Belfort, G. M., Fitzmaurice, H. L., McKinney, R. M., Neve, R. L., Otto, T., & Lin, Y. (2011) · Science · doi:10.1126/science.1208049 · Cited by 295 · see citing works
Munhoz, C. D., Lepsch, L. B., Kawamoto, E. M., Malta, M. B., Lima, L. D. S., Werneck Avellar, M. C., Sapolsky, R. M., & Scavone, C. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4398-05.2006 · Cited by 274 · see citing works
Sutherland, B. W., Toews, J., & Kast, J. (2008) · Journal of Mass Spectrometry · doi:10.1002/jms.1415 · Cited by 273 · see citing works
Chronic Psychological Distress and Risk of Alzheimer’s Disease in Old Age
Wilson, R. S., Arnold, S. E., Schneider, J. A., Kelly, J. F., Tang, Y., & Bennett, D. A. (2006) · Neuroepidemiology · doi:10.1159/000095761 · Cited by 266 · see citing works
Aymard, F., Aguirrebengoa, M., Guillou, E., Javierre, B. M., Bugler, B., Arnould, C., Rocher, V., Iacovoni, J. S., Biernacka, A., Skrzypczak, M., et al. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3387 · Cited by 263 · see citing works
Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability
Meng, F., Du, Z., Alexander Joel Federation, Hu, J., Wang, Q., Kieffer-Kwon, K.-R., Meyers, R. M., Amor, C., Wasserman, C. R., Neuberg, D. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.014 · Cited by 252 · see citing works
Kawashima, T., Okuno, H., Nonaka, M., Adachi-Morishima, A., Yagishita-Kyo, N., Okamura, M., Takemoto‐Kimura, S., Worley, P. F., & Bito, H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806518106 · Cited by 251 · see citing works
Sordet, O., Redon, C. E., Guirouilh‐Barbat, J., Smith, S. H., Solier, S., Douarre, C., Conti, C., Nakamura, A., Das, B. B., Nicolas, E., et al. (2009) · EMBO Reports · doi:10.1038/embor.2009.97 · Cited by 239 · see citing works
A Role for H3K4 Monomethylation in Gene Repression and Partitioning of Chromatin Readers
Cheng, J., Blum, R., Bowman, C., Hu, D., Shilatifard, A., Shen, S., & Dynlacht, B. D. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.02.032 · Cited by 236 · see citing works
Do DNA Double-Strand Breaks Drive Aging?
White, R. R., & Vijg, J. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.08.004 · Cited by 232 · see citing works
Induction of DNA damage, alteration of DNA repair and transcriptional activation by stress hormones
Flint, M. S., Baum, A. E., Chambers, W. H., & Jenkins, F. J. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.02.013 · Cited by 224 · see citing works
Glucocorticoid receptors recruit the CaMKIIα-BDNF-CREB pathways to mediate memory consolidation
Chen, D. Y., Bambah-Mukku, D., Pollonini, G., & Alberini, C. M. (2012) · Nature Neuroscience · doi:10.1038/nn.3266 · Cited by 224 · see citing works
Marley, E. (1962) · Psychopharmacology · doi:10.1007/bf00411372 · Cited by 221 · see citing works
SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability
Ramanan, N., Shen, Y., Sarsfield, S., Lemberger, T., Schütz, G., Linden, D. J., & Ginty, D. D. (2005) · Nature Neuroscience · doi:10.1038/nn1462 · Cited by 218 · see citing works
Early neuronal accumulation of DNA double strand breaks in Alzheimer’s disease
Shanbhag, N. M., Evans, M. D., Mao, W., Nana, A. L., Seeley, W. W., Adame, A., Rissman, R. A., Masliah, E., & Mucke, L. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0723-5 · Cited by 214 · see citing works
Transcriptional elongation requires DNA break-induced signalling
Bunch, H., Lawney, B. P., Lin, Y., Asaithamby, A., Murshid, A., Wang, Y. E., Chen, B. P. C., & Calderwood, S. K. (2015) · Nature Communications · doi:10.1038/ncomms10191 · Cited by 203 · see citing works
RU 38486: A potent antiglucocorticoid in vitro and in vivo
Gagne, D., Pons�, M., & Philibert, D. (1985) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(85)90401-7 · Cited by 187 · see citing works
Genomic integrity and the ageing brain
Chow, H.-M., & Herrup, K. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4020 · Cited by 174 · see citing works
Cristini, A., Ricci, G., Britton, S., Salimbeni, S., Huang, S.-Y. N., Marinello, J., Calsou, P., Pommier, Y. G., Favre, G., Capranico, G., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.041 · Cited by 171 · see citing works
Stress gates an astrocytic energy reservoir to impair synaptic plasticity
Murphy-Royal, C., Johnston, A. D., Boyce, A. K. J., Diaz-Castro, B., Institoris, A., Peringod, G., Zhang, O., Stout, R. F., Spray, D. C., Thompson, R. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15778-9 · Cited by 158 · see citing works
DSBCapture: in situ capture and sequencing of DNA breaks
Lensing, S. V., Marsico, G., Hänsel‐Hertsch, R., Lam, E. Y. N., Tannahill, D., & Balasubramanian, S. (2016) · Nature Methods · doi:10.1038/nmeth.3960 · Cited by 155 · see citing works
Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons
Zada, D., Bronshtein, I., Lerer‐Goldshtein, T., Garini, Y., & Appelbaum, L. (2019) · Nature Communications · doi:10.1038/s41467-019-08806-w · Cited by 154 · see citing works
NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors
Hawk, J. D., Bookout, A. L., Poplawski, S. G., Bridi, M. S., Rao, A. J., Sulewski, M. E., Kroener, B., Manglesdorf, D. J., & Abel, T. G. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64145 · Cited by 147 · see citing works
Wang, Z., Malone, M. H., Thomenius, M. J., Zhong, F., Xu, F., & Distelhorst, C. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303723200 · Cited by 144 · see citing works
Single-cell RNA-seq uncovers a robust transcriptional response to morphine by glia
Avey, D., Sankararaman, S., Yim, A. K. Y., Barve, R., Milbrandt, J., & Mitra, R. D. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.080 · Cited by 143 · see citing works
Revest, J., Roux, A. L., Roullot, V., Kaouane, N., Vallée, M., Kasanetz, F., Rougé‐Pont, F., Tronche, F., Desmedt, A., & Piazza, P. V. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.134 · Cited by 141 · see citing works
The Effect of Acute and Chronic Social Stress on the Hippocampal Transcriptome in Mice
Stankiewicz, A. M., Gościk, J., Majewska, A., Swiergiel, A. H., & Juszczak, G. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142195 · Cited by 138 · see citing works
Iannelli, F., Galbiati, A., Capozzo, I., Nguyen, Q. H., Magnuson, B., Michelini, F., D’Alessandro, G., Cabrini, M., Roncador, M., Francia, S., et al. (2017) · Nature Communications · doi:10.1038/ncomms15656 · Cited by 124 · see citing works
Kelly, E. J., Sandgren, E. P., Brinster, R. L., & Palmiter, R. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10045 · Cited by 118 · see citing works
cAMP Response Element-Binding Protein Is a Primary Hub of Activity-Driven Neuronal Gene Expression
Benito, E., Valor, L. M., Jimenez-Minchan, M., Huber, W. K., & Barco, Á. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4554-11.2011 · Cited by 117 · see citing works
Koyanagi, S., Kusunose, N., Taniguchi, M., Akamine, T., Kanado, Y., Ozono, Y., Masuda, T., Kohro, Y., Matsunaga, N., Tsuda, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13102 · Cited by 117 · see citing works
The Pro-inflammatory Effects of Glucocorticoids in the Brain
Duque, É. D. A., & Munhoz, C. D. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00078 · Cited by 115 · see citing works
Miyata, S., Koyama, Y., Takemoto, K., Yoshikawa, K., Ishikawa, T., Taniguchi, M., Inoue, K., Aoki, M., Hori, O., Katayama, T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019859 · Cited by 114 · see citing works
Morrow, B. A., Elsworth, J. D., Inglis, F. M., & Roth, R. H. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-13-05666.1999 · Cited by 114 · see citing works
Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptomePreprint
Hansen, K. F., Sakamoto, K., Aten, S., Price, K. H., Loeser, J., Hesse, A., Page, C. E., Pelz, C., Arthur, J. S. C., Impey, S., et al. (2016) · Learning & Memory · doi:10.1101/lm.039578.115 · Cited by 107 · see citing works
Seeburg, D. P., & Sheng, M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1853-08.2008 · Cited by 106 · see citing works
O’Meara, R. W., Ryan, S. D., Colognato, H., & Kothary, R. (2011) · Journal of Visualized Experiments · doi:10.3791/3324 · Cited by 103 · see citing works
Belmont, P. J., Tadimalla, A., Chen, W. J., Martindale, J. J., Thuerauf, D. J., Marcinko, M. C., Gude, N. A., Sussman, M. A., & Glembotski, C. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709776200 · Cited by 98 · see citing works
Schwer, B., Wei, P., Chang, A. N., Kao, J., Du, Z., Meyers, R. M., & Alt, F. W. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525564113 · Cited by 97 · see citing works
Two Populations of Glucocorticoid Receptor-Binding Sites in the Male Rat Hippocampal Genome
Polman, J. A. E., de Kloet, E. R., & Datson, N. A. (2013) · Endocrinology · doi:10.1210/en.2012-2187 · Cited by 95 · see citing works
Bellesi, M., Bushey, D., Chini, M., Tononi, G., & Cirelli, C. (2016) · Scientific Reports · doi:10.1038/srep36804 · Cited by 95 · see citing works
Rapid phosphorylation of histone H2A.X following ionotropic glutamate receptor activation
Crowe, S. L., Movsesyan, V. A., Jorgensen, T. J., & Kondratyev, A. D. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04768.x · Cited by 87 · see citing works
Mahfouz, A. E., Lelieveldt, B. P. F., Grefhorst, A., van Weert, L. T. C. M., Mol, I. M., Sips, H. C. M., van den Heuvel, J. K., Datson, N. A., Visser, J. A., Reinders, M. J. T., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520376113 · Cited by 85 · see citing works
Glucocorticoid receptor signaling in astrocytes is required for aversive memory formation
Tertil, M., Skupio, U., Barut, J., Dubovyk, V., Wawrzczak-Bargiela, A., Soltys, Z., Golda, S., Kudla, L., Wiktorowska, L., Szklarczyk, K., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0300-x · Cited by 72 · see citing works
Hollander, J. A., Cory‐Slechta, D. A., Jacka, F. N., Szabo, S. T., Guilarte, T. R., Bilbo, S. D., Mattingly, C. J., Moy, S. S., Haroon, E., Hornig, M., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0648-5 · Cited by 70 · see citing works
Steroid dementia: An overlooked diagnosis?
Sacks, O. W., & Shulman, M. B. (2005) · Neurology · doi:10.1212/01.wnl.0000151977.18440.c3 · Cited by 57 · see citing works
Li, X., Marshall, P. R., Leighton, L. J., Zajaczkowski, E. L., Wang, Z., Madugalle, S. U., Yin, J., Bredy, T. W., & Wei, W. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2024-18.2018 · Cited by 56 · see citing works
Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
Piechota, M., Korostyński, M., Gołda, S., Ficek, J., Jantas, D., Ziółkowska, B., & Przewłocki, R. (2017) · BMC Neuroscience · doi:10.1186/s12868-017-0352-5 · Cited by 52 · see citing works
Choi, M., Ahn, S., Yang, E.-J., Kim, H.-J., Chong, Y. H., & Kim, H. (2016) · Molecular Brain · doi:10.1186/s13041-016-0253-z · Cited by 47 · see citing works
Crowe, S. L., Tsukerman, S., Gale, K., Jorgensen, T. J., & Kondratyev, A. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0092-11.2011 · Cited by 43 · see citing works
DNA Double Strand Breaks: A Common Theme in Neurodegenerative Diseases
Merlo, D., Mollinari, C., Racaniello, M., Garaci, E., & Cardinale, A. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160401114915 · Cited by 42 · see citing works
Fede, G. D., Catania, M., Atzori, C., Moda, F., Pasquali, C., Indaco, A., Grisoli, M., Zuffi, M., Guaita, M. C., Testi, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0656-4 · Cited by 38 · see citing works
Contextual Fear Conditioning Alter Microglia Number and Morphology in the Rat Dorsal Hippocampus
Chaaya, N., Jacques, A., Belmer, A., Beecher, K., Ali, S. A., Chehrehasa, F., Battle, A. R., Johnson, L. R., & Bartlett, S. E. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00214 · Cited by 37 · see citing works
Pooley, J., Flynn, B., Grøntved, L., Baek, S., Guertin, M. J., Kershaw, Y. M., Birnie, M. T., Pellatt, A., Rivers, C. A., Schiltz, R., et al. (2017) · Endocrinology · doi:10.1210/en.2016-1929 · Cited by 27 · see citing works
Transcriptional interference by RNA polymerase III affects expression of the <i>Polr3e</i> gene
Yeganeh, M., Praz, V., Cousin, P., & Hernandez, N. (2017) · Genes & Development · doi:10.1101/gad.293324.116 · Cited by 27 · see citing works
(2009) · Journal of Mass Spectrometry · doi:10.1002/(issn)1096-9888c · Cited by 27 · see citing works
McReynolds, J. R., Taylor, A., Vranjkovic, O., Ambrosius, T., Derricks, O., Nino, B., Kurtoglu, B., Wheeler, R. A., Baker, D., Gasser, P., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.187 · Cited by 26 · see citing works
Heinzmann, J.-M., Thoeringer, C. K., Knapman, A., Palme, R., Holsboer, F., Uhr, M., Landgraf, R., & Touma, C. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02062.x · Cited by 22 · see citing works
Glia: much more than the neuron's side-kick
Stevens, B. A. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00404-4 · Cited by 22 · see citing works
O’Meara, R. W., Ryan, S. D., Colognato, H., & Kothary, R. (2011) · Journal of Visualized Experiments · doi:10.3791/3324-v · Cited by 22 · see citing works
DNA Double-Strand Breaks Are a Critical Regulator of Fear Memory Reconsolidation
Navabpour, S., Rogers, J. M., McFadden, T., & Jarome, T. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238995 · Cited by 20 · see citing works
Boulianne, B., Robinson, M. E., May, P. C., Castellano, L., Blighe, K., Thomas, J., Reid, A. G., Müschen, M., Apperley, J. F., Stebbing, J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.057 · Cited by 17 · see citing works
Recovery from dementia: An interesting case
Knopman, D. S., & Jankowiak, J. (2005) · Neurology · doi:10.1212/wnl.64.4.e18 · Cited by 1 · see citing works
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- [68]Iannelli F, Galbiati A, Capozzo I, Nguyen Q, Magnuson B, Michelini F, et al. A damaged genome’s transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks. Nat Commun. 2017; 8. doi: 10.1038/ncomms15656 28561034 PMC5499205 · DOI
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Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases
Shadfar, S., Parakh, S., Jamali, M. S., & Atkin, J. D. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00350-4 · Cited by 135 · see citing works
“Furthermore, DSBs are now known to form and modify gene expression during physiological neuronal activity [422, 423], which may mediate neuronal plasticity [423].”
BackgroundMechanisms 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
“Stimulating primary neurons with bicuculline or subjecting mice to fear learning results in the induction of DSBs at the promoters of immediate-early genes (Fig 1) (Madabhushi et al , 2015; Stott et al , 2021).”
Self-citationEpigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease
Maity, S., Farrell, K., Navabpour, S., Narayanan, S. N., & Jarome, T. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212280 · Cited by 123 · see citing works
Recombination of repeat elements generates somatic complexity in human genomes
Pascarella, G., Hon, C. C., Hashimoto, K., Busch, A., Luginbühl, J., Parr, C., Hin Yip, W., Abe, K., Kratz, A., Bonetti, A., et al. (2022) · Cell · doi:10.1016/j.cell.2022.06.032 · Cited by 77 · see citing works
The threat of programmed DNA damage to neuronal genome integrity and plasticity
Caldecott, K. W., Ward, M. E., & Nussenzweig, A. (2022) · Nature Genetics · doi:10.1038/s41588-021-01001-y · Cited by 80 · see citing works
Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder
Phan, B. N., Ray, M. H., Xue, X., Fu, C., Fenster, R. J., Kohut, S. J., Bergman, J., Haber, S. N., McCullough, K. M., Fish, M. K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45165-7 · Cited by 56 · see citing works
The Role of DNA Damage in Neural Plasticity in Physiology and Neurodegeneration
Konopka, A., & Atkin, J. D. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.836885 · Cited by 51 · see citing works
“This was also associated with experience-driven transcriptional changes within neurons (Stott et al., 2021).”
BackgroundDNA damage and its links to neuronal aging and degeneration
Delint‐Ramírez, I., & Madabhushi, R. (2025) · Neuron · doi:10.1016/j.neuron.2024.12.001 · Cited by 51 · see citing works
Delint‐Ramírez, I., Konada, L., Heady, L., Rueda, R., Jácome, A. S. V., Marlin, E., Marchioni, C. R., Segev, A., Kritskiy, O., Yamakawa, S., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.09.012 · Cited by 46 · see citing works
Self-citationDNA damage response in neurodevelopment and neuromaintenance
Qing, X., Zhang, G., & Wang, Z. (2022) · FEBS Journal · doi:10.1111/febs.16535 · Cited by 38 · see citing works
DNA Methylation and Establishing Memory
Bernstein, C. (2022) · Epigenetics Insights · doi:10.1177/25168657211072499 · Cited by 39 · see citing works
An Adaptive Role for DNA Double-Strand Breaks in Hippocampus-Dependent Learning and Memory
Boutros, S. W., Unni, V. K., & Raber, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158352 · Cited by 29 · see citing works
“These upregulated genes are primarily related to cellular homeostasis, cell motility and adhesion, and proliferation and cell death, again indicating the specificity of DSBs for the type of stimulus [69].”
BackgroundInfluentialTopoisomerase-Mediated DNA Damage in Neurological Disorders
Crewe, M., & Madabhushi, R. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.751742 · Cited by 24 · see citing works
Bhatia, S., Arslan, E. P., Rodriguez-Hernandez, L. D., Bonin, R. P., & Wells, P. G. (2022) · Toxicological Sciences · doi:10.1093/toxsci/kfac003 · Cited by 21 · see citing works
Segev, A., Heady, L., Crewe, M., & Madabhushi, R. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113809 · Cited by 14 · see citing works
Perneel, J., Osua, M. L., Alidadiani, S., Peeters, N., Witte, L. D., Heeman, B., Manzella, S., Rycke, R. M. D., Brooks, M., Perkerson, R. B., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00831-2 · Cited by 13 · see citing works
“1700016P03Rik, encoding miR132 and miR212 [62, 63], which downregulates TMEM106B [22] and which has consistently been downregulated in neurodegenerative diseases [29].”
Ranganathan, R., Sapozhnikov, G., Wang, N., Li, S., & Song, Y. (2023) · Translational Medicine of Aging · doi:10.1016/j.tma.2023.06.004 · Cited by 13 · see citing works
DNA Damage and Chromatin Rearrangement Work Together to Promote Neurodegeneration
Sharma, H., Koirala, S., Chew, Y. L., & Konopka, A. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04331-0 · Cited by 14 · see citing works
“Interest-ingly, DNA damage is also associated with cognitive processes [31].”
BackgroundBelloy, M., Schmitt, B., Marty, F., Paut, C., Bassot, E., Aïda, A., Alis, M., Zahm, M., Chaubet, A., Garnier, H., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02041-x · Cited by 11 · see citing works
“Like defective DNA repair, which causes cognitive deficits 15,16 , the absence of breakage of the DNA during learning processes also impairs memory formation 14,28,38,39 .”
Jiao, X., Sante, G. D., Casimiro, M. C., Tantos, Á., Ashton, A. W., Li, Z., Quach, Y., Bhargava, D. K., Rocco, A. D., Pupo, C., et al. (2024) · Oncogenesis · doi:10.1038/s41389-023-00502-1 · Cited by 10 · see citing works
Boutros, S. W., Zimmerman, B., Nagy, S. C., Unni, V. K., & Raber, J. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01966-8 · Cited by 9 · see citing works
“We did not observe increases in DSBs post-training, likely due to differences in γ H2Ax and 53BP1 function and kinetics, nor increases in DSB-associated IEGs after fear conditioning as reported by others [52, 100].”
BackgroundResultShishido, R., Kunii, Y., Hino, M., Izumi, R., Nagaoka, A., Hayashi, H., Kakita, A., Tomita, H., & Yabe, H. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1183696 · Cited by 9 · see citing works
Bridging the gap: R-loop mediated genomic instability and its implications in neurological diseases
Westover, K. R., Jin, P., & Yao, B. (2024) · Epigenomics · doi:10.2217/epi-2023-0379 · Cited by 9 · see citing works
Recombination of repeat elements generates somatic complexity in human genomesPreprint
Pascarella, G., Hashimoto, K., Busch, A., Luginbühl, J., Parr, C., Hon, C.-C., Yip, W. H., Abe, K., Kratz, A., Bonetti, A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.02.163816 · Cited by 8 · see citing works
“, 2005), although at present it is unknown whether NAHR of repeat elements may participate in the repair of DNA DSBs generated during the activation of developmental programs and even by normal brain physiology (Stott et al., 2021).”
BackgroundZ-DNA and Z-RNA: Methods—Past and Future
Herbert, A. G. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3084-6_21 · Cited by 7 · see citing works
Brain Metabolic DNA: A Long Story and Some Conclusions
Giuditta, A., Zucconi, G. G., & Sadile, A. G. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03030-y · Cited by 5 · see citing works
On the origin and nature of nongenetic information in eumetazoans
Cabej, N. R. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.15001 · Cited by 5 · see citing works
Novel Techniques for Mapping DNA Damage and Repair in the Brain
Hedlich-Dwyer, J., Allard, J. S., Mulgrave, V. E., Kisby, G. E., Raber, J., & Gassman, N. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137021 · Cited by 4 · see citing works
“…to the prefrontal cortex and hippocampal regions also identified increased DSB induced by contextual fear conditioning across these regions, with clusters of damage observed in genes associated with synaptic processes, early response genes, RNA-binding genes, and cytoskeleton-related genes [2].”
BackgroundBordin, D. L., Lefol, Y., Lagartos-Donate, M. J., Montaldo, N. P., Rolseth, V., Tekin, N. B., Lirussi, L., Neurauter, C. G., Liu, Y., Aman, Y., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf722 · Cited by 4 · see citing works
“Programmed DNA breaks are also introduced in several types of neurons, e.g. during learning [ 2 ] and cell specification [ 3 , 4 ].”
Mobile circular DNAs regulating memory and communication in CNS neurons
Smalheiser, N. R. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1304667 · Cited by 4 · see citing works
Adaptive and Maladaptive DNA Breaks in Neuronal Physiology and Alzheimer’s Disease
Roberts, A., Swerdlow, R. H., & Wang, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147774 · Cited by 4 · see citing works
“…the relationship between DNA break formation and IEG response in vivo by using contextual fear conditioning (CFC), which subjects mice to a novel environment with an adverse stimulus and, utilizing ChIP-Seq, revealed a rapid induction of DNA breaks within 30 min post-neuronal stimulus [34].”
BackgroundResultInfluentialJhanji, M., Bhan, A., Arrowood, C. A., Yakout, D. W., Shroff, A., McManus, D., Gifford, H., Vacharasin, J. M., Lizarraga, S. B., Nazarko, T. Y., et al. (2025) · IUBMB Life · doi:10.1002/iub.70030 · Cited by 4 · see citing works
“Since neuronal activity-induced DNA damage and associated transcription are essential for memory formation [35, 39, 76, 79, 80], together, these results suggest that tyrosine and phenylalanine-mediated activation of neuronal DNA repair might contribute to AD development.”
Lu, L.-F., Wang, J., Liu, K.-Z., Yi, X., Ma, Z.-J., Li, Y., & Feng, R. (2022) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2022.103292 · Cited by 4 · see citing works
Boutros, S. W., Kessler, K., Unni, V. K., & Raber, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-17052-y · Cited by 3 · see citing works
Characterization of dUTPase expression in mouse postnatal development and adult neurogenesis
Nagy, N. T., Hádinger, N., Tóth, O., Rácz, G. A., Pintér, T., Gál, Z., Urbán, M., Gócza, E., Hiripi, L., Acsády, L., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-63405-0 · Cited by 3 · see citing works
Shcherbinina, V., Даев, Е. В., Pavlova, M. B., & Dyuzhikova, N. A. (2024) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-024-01692-w · Cited by 3 · see citing works
“The mechanisms for neuronal DSBs generation have been actively studied and to the present day include aberrant activation of endonucleases, dephosphorylation of Top2B, convergent transcription, oxidative stress, and inhibition of DNA repair machinery [7, 25, 26].”
Hou, Y., Park, J. H., Dan, X., Chu, X., Yang, B., Hussain, M., Croteau, D. L., & Bohr, V. A. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106092 · Cited by 3 · see citing works
NPAS4 juggles neuronal activity-dependent transcription and DSB repair with NuA4
Delint‐Ramírez, I., & Madabhushi, R. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.03.019 · Cited by 3 · see citing works
Vijayakumar, S., Yesudhason, B. V., Anandharaj, J. L., Vedakumari, S. W., & Christyraj, J. R. S. S. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09693-1 · Cited by 4 · see citing works
“Researchers have used cH2AX chromatin immunoprecipitation (ChIP) sequencing to determine the activation of DSBs at immediate-early gene promoters [64, 65].”
The Roles of Topoisomerases in Transcriptional Regulation
Fenelon, K. D., & Madabhushi, R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031552 · Cited by 2 · see citing works
“…DSBs are enriched within promoters of neuronal early response genes (ERGs), such as Fos , Npas4 , Egr1 , Nr4a1 , and Arc , whose products mediate experience-dependent synaptic changes and the development of lasting adaptive behaviors, such as learning and long-term memory formation [109,178–180].”
Ranganathan, R., Li, S., Sapozhnikov, G., Wang, S., & Song, Y. (2025) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823241296018 · Cited by 2 · see citing works
Heady, L., Rueda, R., Segev, A., Morton, K. G., & Madabhushi, R. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.06.652469 · Cited by 2 · see citing works
Potential Contribution of Retrotransposons to Learning and Memory
Glanzman, D. L. (2024) · Springer eBooks · doi:10.1007/978-3-031-59286-7_12 · Cited by 1 · see citing works
Transcriptional and epigenetic regulation of memory storage
Abel, T. G., Basu, B., & Chatterjee, S. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00076-6 · Cited by 1 · see citing works
Belloy, M., Schmitt, B. A. M., Marty, F. H., Paut, C., Emilie, B.-P., Aïda, A., Alis, M., Ecalard, R., Boursereau, R., Gonzalez‐Dunia, D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.03.578747 · Cited by 1 · see citing works
Memories are made by breaking DNA — and fixing it
Kozlov, M. (2024) · Nature · doi:10.1038/d41586-024-00930-y · Cited by 1 · see citing works
The double-edged sword of the double-stranded break
Fenster, R. J., & Suh, J. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01403-4
“X was subsequently shown to occur in vivo, in several different neuron types, in response to both physiological and optogenetic stimulation [4].”
BackgroundBruter, C. P. (2023) · Entropie thermodynamique – énergie – environnement – économie · doi:10.21494/iste.op.2023.0982
Abdelmageed, M., Palanisamy, P., Vernail, V. L., Silberman, Y., Paul, S., & Paul, A. (2024) · eLife · doi:10.1101/2023.09.27.559771 · Cited by 1 · see citing works
Abdelmageed, M., Palanisamy, P., Vernail, V. L., Silberman, Y., Paul, S., & Paul, A. (2024) · eLife · doi:10.7554/elife.101533.1
Perturbations to Stimulus-Dependent Gene Activity Patterns in Neurodegenerative Disorders
Madabhushi, R., & Tsai, L. (2024) · Springer eBooks · doi:10.1007/978-3-031-68550-7_15
Self-citationHistone Variants in Neuronal Transcription and Behavioral Regulation
McLean, T. A. B., Walters, B. J., & Zovkic, I. B. (2024) · Springer eBooks · doi:10.1007/978-3-031-68550-7_6
DNA Damage, Repair, and Advanced DNA Damage Detection Technologies
Hernandez, A., Goel, K., Hussain, S., & Gassman, N. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00179-0
Solntseva, S. V., Efimova, O., & Nikitin, V. P. (2024) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-024-06274-x
“Thus, in studies on non-nerve tissues, it was shown that reparation of double-strand breaks can result in the formation of extrachromosomal circular DNA [13].”
Abdelmageed, M., Palanisamy, P., Vernail, V. L., Silberman, Y., Paul, S., & Paul, A. (2026) · eLife · doi:10.7554/elife.101533.2
Maio, N., & Rouault, T. A. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113129
Nongenetic Mechanisms of Animal Evolution
Cabej, N. R. (2026) · Springer eBooks · doi:10.1007/978-3-032-24295-2_27
Konada, L., Catley, T. E., Heady, L., Crewe, M., Delint‐Ramírez, I., Wiggins, L., Briseno, S. F., Bhat, M. Y., Segev, A., Pyne, A. L. B., et al. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.05.014
Kumar, C. G., Rao, G. M., Rai, R., Murlimanju, B. V., & Blossom, V. (2026) · Journal of Anatomical Society of India · doi:10.4103/jasi.jasi_31_26
Shcherbinina, V., Прибышина, А. К., Baranova, K. A., Pavlova, M. B., & Dyuzhikova, N. A. (2026) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-026-02091-z
Crewe, M., Pope, A., Delint‐Ramírez, I., Briseno, S. F., Stott, R. T., Tsai, L.-H., Huber, K. M., & Madabhushi, R. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118152
Self-citationHeady, L., Fenelon, K. D., Delint‐Ramírez, I., Rueda, R., Segev, A., Morton, K. G., Briseno, S. F., & Madabhushi, R. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118186
- Authors
- Stott, R. T., Kritsky, O., & Tsai, L.-H.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Tsai, Li-Huei
- ORCID
- Tsai, Li-Huei
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2021-07-01
- Volume
- 16
- Issue
- 7
- Pages
- e0249691
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC8248687
- OpenAlex
- W3137582618
- Cited by
- 62
- References
- 144
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 20 · 2023: 10 · 2022: 13 · 2021: 2 · 2020: 1
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (R01NS102730-01)
- Glenn Foundation for Medical Research
- JPB Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA double-strand breaks, contextual fear conditioning, neuronal activity, early response genes, γH2AX, medial prefrontal cortex, hippocampus, synaptic activity, glucocorticoids, glial cells, proteostasis, transcriptional regulation
- MeSH terms
- Proteostasis, Chromatin Immunoprecipitation Sequencing, Animals, Fear, Hippocampus, Histones, Male, Mice, Inbred C57BL, Neurons, Prefrontal Cortex, 3' Untranslated Regions, Mice, DNA Breaks, Double-Stranded
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