Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells
Open accessAbstract
Repair of DNA double-strand breaks (DSBs) by non-homologous end joining is critical for neural development, and brain cells frequently contain somatic genomic variations that might involve DSB intermediates. We now use an unbiased, high-throughput approach to identify genomic regions harboring recurrent DSBs in primary neural stem/progenitor cells (NSPCs). We identify 27 recurrent DSB clusters (RDCs), and remarkably, all occur within gene bodies. Most of these NSPC RDCs were detected only upon mild, aphidicolin-induced replication stress, providing a nucleotide-resolution view of replication-associated genomic fragile sites. The vast majority of RDCs occur in long, transcribed, and late-replicating genes. Moreover, almost 90% of identified RDC-containing genes are involved in synapse function and/or neural cell adhesion, with a substantial fraction also implicated in tumor suppression and/or mental disorders. Our characterization of NSPC RDCs reveals a basis of gene fragility and suggests potential impacts of DNA breaks on neurodevelopment and neural functions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Long-neural genes with synaptic and cell adhesion genes associated with the recurrent DNA double-strand breaks and AD GWAS genes are enriched for gene fusions.
“Indeed, we find that long-neural genes with synaptic and cell adhesion genes associated with the recurrent DNA double-strand breaks and AD GWAS genes are enriched for gene fusions 73.”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [73]
The genomic location of DNA damage impacts neuronal activity and degeneration.
“we are just beginning to appreciate the significance of a lesion’s genomic location in relation to its effect on neuronal activity and, ultimately, degeneration”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Wei et al, 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
Lieber, M. R. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.052308.093131 · Cited by 2,882 · see citing works
Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters
Core, L. J., Waterfall, J. J., & Lis, J. T. (2008) · Science · doi:10.1126/science.1162228 · Cited by 1,986 · see citing works
Identification of a Chromosome 18q Gene that Is Altered in Colorectal Cancers
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., et al. (1990) · Science · doi:10.1126/science.2294591 · Cited by 1,738 · see citing works
A clustering approach for identification of enriched domains from histone modification ChIP-Seq data
Zang, C., Schones, D. E., Zeng, C., Cui, K., Zhao, K., & Peng, W. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp340 · Cited by 1,043 · see citing works
Topologically associating domains are stable units of replication-timing regulation
Pope, B. D., Ryba, T., Dileep, V., Yue, F., Wu, W.-S., Denas, O., Vera, D. L., Wang, Y., Hansen, R. S., Canfield, T. K., et al. (2014) · Nature · doi:10.1038/nature13986 · Cited by 902 · see citing works
Subgroup-specific structural variation across 1,000 medulloblastoma genomes
Northcott, P. A., Shih, D. J. H., Peacock, J., Garzia, L., Morrissy, A. S., Zichner, T., Stütz, A. M., Korshunov, A., Reimand, J., Schumacher, S. E., et al. (2012) · Nature · doi:10.1038/nature11327 · Cited by 887 · see citing works
Rausch, T., Jones, D. T. W., Zapatka, M., Stütz, A. M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P. A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.013 · Cited by 865 · 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
Transposition and amplification of oncogene-related sequences in human neuroblastomas
Kohl, N. E., Kanda, N., Schreck, R. R., Bruns, G. A. P., Latt, S. A., Gilbert, F., & Alt, F. W. (1983) · Cell · doi:10.1016/0092-8674(83)90169-1 · Cited by 729 · see citing works
Durkin, S. G., & Glover, T. W. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.042007.165900 · Cited by 715 · 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
A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis
Gao, Y., Sun, Y., Frank, K. M., Dikkes, P., Fujiwara, Y., Seidl, K. J., Sekiguchi, J. M., Rathbun, G. A., Swat, W., Wang, J., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81714-6 · Cited by 688 · see citing works
Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases
Frock, R. L., Hu, J., Meyers, R. M., Ho, Y.-J., Kii, E., & Alt, F. W. (2015) · Nature Biotechnology · doi:10.1038/nbt.3101 · Cited by 673 · see citing works
Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development
Gao, Y., Ferguson, D., Xie, W., Manis, J., Sekiguchi, J., Frank, K., Chaudhuri, J., Horner, J., DePinho, R., & Alt, F. (2000) · Nature · doi:10.1038/35009138 · Cited by 608 · see citing works
Ryba, T., Hiratani, I., Lu, J., Itoh, M., Kulik, M. J., Zhang, J., Schulz, T. C., Robins, A. J., Dalton, S., & Gilbert, D. M. (2010) · Genome Research · doi:10.1101/gr.099655.109 · Cited by 608 · see citing works
Glover, T. W., Berger, C. S., Coyle-Morris, J. F., & Echo, B. (1984) · Human Genetics · doi:10.1007/bf00272988 · Cited by 604 · see citing works
Somatic mutation, genomic variation, and neurological disease
Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013) · Science · doi:10.1126/science.1237758 · Cited by 584 · see citing works
Helmrich, A., Ballarino, M., & Tora, L. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.10.013 · Cited by 576 · see citing works
Mosaic Copy Number Variation in Human Neurons
McConnell, M. J., Lindberg, M. R., Brennand, K. J., Piper, J. C., Voet, T., Cowing-Zitron, C., Shumilina, S., Lasken, R. S., Vermeesch, J. R., Hall, I. M., et al. (2013) · Science · doi:10.1126/science.1243472 · Cited by 551 · see citing works
Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation
Hiratani, I., Ryba, T., Itoh, M., Yokochi, T., Schwaiger, M., Chang, C., Lyou, Y., Townes, T. M., Schübeler, D., & Gilbert, D. M. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060245 · Cited by 548 · see citing works
Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal Translocations
Zhang, Y., McCord, R. P., Ho, Y.-J., Lajoie, B. R., Hildebrand, D. G., Simon, A. C., Becker, M. S., Alt, F. W., & Dekker, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.002 · Cited by 545 · see citing works
Frank, K. M., Sharpless, N. E., Gao, Y., Sekiguchi, J., Ferguson, D. O., Zhu, C., Manis, J. P., Horner, J. W., DePinho, R. A., & Alt, F. W. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80264-6 · Cited by 492 · see citing works
Mechanisms of Programmed DNA Lesions and Genomic Instability in the Immune System
Alt, F. W., Zhang, Y., Meng, F., Guo, C., & Schwer, B. (2013) · Cell · doi:10.1016/j.cell.2013.01.007 · Cited by 477 · see citing works
Aguilera, A., & García-Muse, T. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-111212-133232 · Cited by 476 · see citing works
Chiarle, R., Zhang, Y., Frock, R. L., Lewis, S. M., Molinié, B., Ho, Y.-J., Myers, D. R., Choi, V. W., Compagno, M., Malkin, D. J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.07.049 · Cited by 475 · see citing works
Paull, T. T. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034335 · Cited by 458 · see citing works
Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice
Barnes, D. E., Stamp, G., Rosewell, I. R., Denzel, A., & Lindahl, T. L. (1998) · Current Biology · doi:10.1016/s0960-9822(98)00021-9 · Cited by 438 · see citing works
Identification of Early Replicating Fragile Sites that Contribute to Genome Instability
Barlow, J. H., Faryabi, R. B., Callén, E., Wong, N., Malhowski, A. J., Chen, H. T., Gutierrez-Cruz, G., Sun, H., McKinnon, P. J., Wright, G. W., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.006 · Cited by 433 · see citing works
Zhu, C., Mills, K. D., Ferguson, D. O., Lee, C., Manis, J., Fleming, J., Gao, Y., Morton, C. C., & Alt, F. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00770-5 · Cited by 421 · cited 2× · see citing works
“…which routinely develop lethal progenitor B cell lymphomas with clonal translocations and amplifications involving fusion of V(D)J recombination-associated DSBs in the immunoglobulin heavychain (IgH) and c-myc oncogene loci via A-EJ (Difilippantonio et al., 2002; Hu et al., 2015; Zhu et al., 2002).”
Klein, I. A., Resch, W., Janković, M., Oliveira, T. Y., Yamane, A., Nakahashi, H., Virgilio, M. D., Bothmer, A., Nussenzweig, A., Robbiani, D. F., et al. (2011) · Cell · doi:10.1016/j.cell.2011.07.048 · Cited by 353 · see citing works
Transcription as a source of genome instability
Kim, N., & Jinks-Robertson, S. (2012) · Nature reviews genetics · doi:10.1038/nrg3152 · Cited by 297 · see citing works
Boboilă, C., Alt, F. W., & Schwer, B. (2012) · Advances in immunology · doi:10.1016/b978-0-12-394300-2.00001-6 · Cited by 273 · see citing works
Generation of neuronal variability and complexity
Muotri, A. R., & Gage, F. H. (2006) · Nature · doi:10.1038/nature04959 · Cited by 271 · see citing works
Mobile DNA elements in the generation of diversity and complexity in the brain
Erwin, J. A., Marchetto, M. C., & Gage, F. H. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3730 · Cited by 264 · 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
Maintaining genome stability in the nervous system
McKinnon, P. J. (2013) · Nature Neuroscience · doi:10.1038/nn.3537 · Cited by 229 · see citing works
Difilippantonio, M. J., Petersen, S., Chen, H. T., Johnson, R., Jasin, M., Kanaar, R., Ried, T., & Nussenzweig, A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020851 · Cited by 225 · see citing works
Tallec, B. L., Millot, G. A., Blin, M., Brison, O., Dutrillaux, B., & Debatisse, M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.003 · Cited by 188 · see citing works
Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes
Hu, J., Zhang, Y., Zhao, L., Frock, R. L., Du, Z., Meyers, R. M., Meng, F., Schatz, D. G., & Alt, F. W. (2015) · Cell · doi:10.1016/j.cell.2015.10.016 · Cited by 157 · see citing works
Molecular profiling of common fragile sites in human fibroblasts
Tallec, B. L., Dutrillaux, B., Lachagès, A.-M., Millot, G. A., Brison, O., & Debatisse, M. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2155 · Cited by 127 · see citing works
Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching
Dong, J., Panchakshari, R. A., Zhang, T., Zhang, Y., Hu, J., Volpi, S. A., Meyers, R. M., Ho, Y.-J., Du, Z., Robbiani, D. F., et al. (2015) · Nature · doi:10.1038/nature14970 · Cited by 123 · see citing works
Self-citationDNA ligase IV suppresses medulloblastoma formation.
Lee, Y., & McKinnon, P. J. (2002) · PubMed · Cited by 122 · see citing works
XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice
Yan, C. T., Kaushal, D., Murphy, M., Zhang, Y., Datta, A., Chen, C., Monroe, B., Mostoslavsky, G., Coakley, K. M., Gao, Y., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601938103 · Cited by 117 · see citing works
Helmrich, A., Stout‐Weider, K., Hermann, K., Schröck, E., & Heiden, T. (2006) · Genome Research · doi:10.1101/gr.5335506 · Cited by 105 · see citing works
Antibody Class Switching Mediated by Yeast Endonuclease-Generated DNA Breaks
Zarrin, A. A., Fitz, C. D. V., Tseng, E., Gleason, M., Zarin, P., Tian, M., & Alt, F. W. (2006) · Science · doi:10.1126/science.1136386 · 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
Krummel, K. A., Denison, S. R., Calhoun, E. S., Phillips, L. A., & Smith, D. I. (2002) · Genes Chromosomes and Cancer · doi:10.1002/gcc.10047 · Cited by 85 · see citing works
Weddington, N., Stuy, A., Hiratani, I., Ryba, T., Yokochi, T., & Gilbert, D. M. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-530 · Cited by 83 · see citing works
Updating the mechanisms of common fragile site instability: how to reconcile the different views?
Tallec, B. L., Koundrioukoff, S., Wilhelm, T., Letessier, A., Brison, O., & Debatisse, M. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1720-2 · Cited by 65 · see citing works
Arlt, M. F., Rajendran, S., Birkeland, S. R., Wilson, T. E., & Glover, T. W. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002981 · Cited by 56 · see citing works
Unique and redundant functions of ATM and DNA-PKcs during V(D)J recombination
Gapud, E. J., & Sleckman, B. P. (2011) · Cell Cycle · doi:10.4161/cc.10.12.16011 · Cited by 54 · see citing works
Very large common fragile site genes and their potential role in cancer development
Gao, G., & Smith, D. I. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1753-6 · Cited by 39 · see citing works
Characterization of FRA7B, a human common fragile site mapped at the 7p chromosome terminal region
Bosco, N., Pelliccia, F., & Rocchi, A. R. (2010) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2010.06.008 · Cited by 35 · see citing works
Savelyeva, L., & Brueckner, L. M. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1723-z · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Endogenous DNA damage as a source of genomic instability in cancer
Tubbs, A., & Nussenzweig, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.002 · Cited by 1,452 · see citing works
The role of adult hippocampal neurogenesis in brain health and disease
Toda, T., Parylak, S. L., Linker, S. B., & Gage, F. H. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0036-2 · Cited by 719 · see citing works
Genetic insights into the neurodevelopmental origins of schizophrenia
Birnbaum, R., & Weinberger, D. R. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.125 · Cited by 493 · see citing works
Conflict Resolution in the Genome: How Transcription and Replication Make It Work
Hamperl, S., & Cimprich, K. A. (2016) · Cell · doi:10.1016/j.cell.2016.09.053 · Cited by 275 · 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
Hu, J., Meyers, R. M., Dong, J., Panchakshari, R. A., Alt, F. W., & Frock, R. L. (2016) · Nature Protocols · doi:10.1038/nprot.2016.043 · Cited by 261 · see citing works
Mosaicism in health and disease — clones picking up speed
Forsberg, L. A., Gisselsson, D., & Dumanski, J. P. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.145 · Cited by 253 · see citing works
McConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., Erwin, J. A., Fasching, L., Flasch, D. A., Freed, D., et al. (2017) · Science · doi:10.1126/science.aal1641 · Cited by 262 · see citing works
Fragile sites in cancer: more than meets the eye
Glover, T. W., Wilson, T. E., & Arlt, M. F. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.52 · Cited by 247 · see citing works
Popova, G., Soliman, S. S., Kim, C. N., Keefe, M. G., Hennick, K. M., Jain, S., Li, T., Tejera, D., Shin, D. S., Chhun, B. B., et al. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.08.015 · Cited by 237 · see citing works
Somatic APP gene recombination in Alzheimer’s disease and normal neurons
Lee, M.-H., Siddoway, B., Kaeser, G. E., Segota, I., Rivera, R., Romanow, W. J., Liu, C. S., Park, C., Kennedy, G., Long, T., et al. (2018) · Nature · doi:10.1038/s41586-018-0718-6 · Cited by 210 · see citing works
DNA polymerase θ (POLQ), double-strand break repair, and cancer
Wood, R. D., & Doublié, S. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.05.003 · Cited by 214 · see citing works
A large data resource of genomic copy number variation across neurodevelopmental disorders
Zarrei, M., Burton, C. L., Engchuan, W., Young, E. J., Higginbotham, E. J., MacDonald, J. R., Trost, B., Chan, A. J. S., Walker, S., Lamoureux, S., et al. (2019) · npj Genomic Medicine · doi:10.1038/s41525-019-0098-3 · Cited by 187 · see citing works
Carruthers, R., Ahmed, S. U., Ramachandran, S., Strathdee, K. E., Kurian, K. M., Hedley, A., Gomez-Roman, N., Kalna, G., Neilson, M., Gilmour, L., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0569 · Cited by 180 · see citing works
Transcription-Coupled DNA Double-Strand Break Repair: Active Genes Need Special Care
Marnef, A., Cohen, S., & Legube, G. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.03.024 · Cited by 138 · see citing works
High-resolution copy number variation analysis of schizophrenia in Japan
Kushima, I., Aleksić, B., Nakatochi, M., Shimamura, T., Shiino, T., Yoshimi, A., Kimura, H., Takasaki, Y., Wang, C., Xing, J., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.88 · Cited by 132 · see citing works
Dileep, V., Boix, C. A., Mathys, H., Marco, A., Welch, G. M., Meharena, H. S., Loon, A., Jeloka, R., Peng, Z., Bennett, D. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.038 · Cited by 130 · 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
Ghouzzi, V. E., Bianchi, F. T., Molineris, I., Mounce, B. C., Berto, G. E., Rak, M., Lebon, S., Aubry, L., Tocco, C., Gai, M., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.266 · Cited by 128 · see citing works
Nesta, A. V., Tafur, D., & Beck, C. R. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.10.003 · Cited by 126 · see citing works
Replication stress impairs chromosome segregation and preimplantation development in human embryos
Palmerola, K. L., Amrane, S., Angeles, A. D. L., Xu, S., Wang, N., de Pinho, J., Zuccaro, M. V., Taglialatela, A., Massey, D. J., Turocy, J. M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.06.028 · Cited by 124 · see citing works
Environmental change drives accelerated adaptation through stimulated copy number variation
Hull, R. M., Cruz, C., Jack, C. V., & Houseley, J. M. (2017) · PLoS Biology · doi:10.1371/journal.pbio.2001333 · Cited by 123 · see citing works
Amente, S., Di Palo, G., Scala, G., Castrignanò, T., Gorini, F., Cocozza, S., Moresano, A., Pucci, P., Ma, B., Stepanov, I., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1152 · Cited by 123 · see citing works
Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons
Reid, D. A., Reed, P. J., Schlachetzki, J. C. M., Nitulescu, I. I., Chou, G., Tsui, E. C., Jones, J. R., Chandran, S., Lu, A. T., McClain, C. A., et al. (2021) · Science · doi:10.1126/science.abb9032 · Cited by 121 · see citing works
DNA double-strand breaks as drivers of neural genomic change, function, and disease
Alt, F. W., & Schwer, B. (2018) · DNA Repair · doi:10.1016/j.dnarep.2018.08.019 · Cited by 110 · see citing works
The role of chromatin loop extrusion in antibody diversification
Zhang, Y., Zhang, X., Dai, H., Hu, H., & Alt, F. W. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00679-3 · Cited by 106 · see citing works
Kumar, V., Alt, F. W., & Frock, R. L. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1611882113 · Cited by 106 · see citing works
Wang, M., Wei, P.-C., Lim, C. K., Gallina, I. S., Marshall, S., Marchetto, M. C., Alt, F. W., & Gage, F. H. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.12.013 · Cited by 105 · see citing works
Genomic mosaicism in the developing and adult brain
Rohrback, S., Siddoway, B. A., Liu, C. S., & Chun, J. J. M. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22626 · Cited by 103 · see citing works
Gabriele, M., Lopez Tobon, A., D'Agostino, G., & Testa, G. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.12.013 · Cited by 103 · 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
Transcription-dependent regulation of replication dynamics modulates genome stability
Blin, M., Tallec, B. L., Nähse, V., Schmidt, M., Brossas, C., Millot, G. A., Prioleau, M., & Debatisse, M. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0170-1 · Cited by 98 · see citing works
Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing
Yin, J., Lu, R., Xin, C., Wang, Y., Ling, X., Li, D., Zhang, W., Liu, M., Xie, W., Kong, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28900-w · Cited by 95 · see citing works
Xiong, F., Wang, R., Lee, J.-H., Li, S., Chen, S.-F., Liao, Z., Hasani, L. A., Nguyen, P. T.-M., Zhu, X., Krakowiak, J., et al. (2021) · Cell Research · doi:10.1038/s41422-021-00515-8 · Cited by 96 · see citing works
Puget, N., Miller, K. M., & Legube, G. (2019) · DNA repair · doi:10.1016/j.dnarep.2019.102661 · Cited by 90 · see citing works
Sugino, K., Clark, E., Schulmann, A., Shima, Y., Wang, L., Hunt, D. L., Hooks, B. M., Tränkner, D., Chandrashekar, J., Picard, S., et al. (2019) · eLife · doi:10.7554/elife.38619 · Cited by 84 · see citing works
Devhare, P. B., Meyer, K., Steele, R., Ray, R. B., & RAY, R. K. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.517 · Cited by 85 · see citing works
Replication stress induces accumulation of FANCD2 at central region of large fragile genes
Okamoto, Y., Iwasaki, W. M., Kugou, K., Takahashi, K., Oda, A., Sato, K., Kobayashi, W., Kawai, H., Sakasai, R., Takaori‐Kondo, A., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky058 · Cited by 89 · see citing works
When Genome Maintenance Goes Badly Awry
Kass, E. M., Moynahan, M. E., & Jasin, M. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.021 · Cited by 83 · see citing works
Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors
Ratnaparkhe, M., Wong, J., Wei, P., Hlevnjak, M., Kolb, T., Simovic-Lorenz, M., Haag, D., Paul, Y., Devens, F., Northcott, P. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06925-4 · Cited by 83 · 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
A Upf3b-mutant mouse model with behavioral and neurogenesis defects
Huang, L., Shum, E. Y., Jones, S. H., Lou, C.-H., Chousal, J. N., Kim, H. Y., Roberts, A. J., Jolly, L. A., Espinoza, J. L., Skarbrevik, D., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.173 · Cited by 79 · see citing works
Rasmussen, K. L., Tybjærg‐Hansen, A., Nordestgaard, B. G., & Frikke‐Schmidt, R. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.05.006 · Cited by 75 · see citing works
Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex
Chronister, W. D., Burbulis, I. E., Wierman, M. B., Wolpert, M. J., Haakenson, M. F., Smith, A. C. B., Kleinman, J. E., Hyde, T. M., Weinberger, D. R., Bekiranov, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.107 · Cited by 72 · see citing works
Mokretar, K., Pease, D., Taanman, J., Soenmez, A., Ejaz, A., Lashley, T., Ling, H., Gentleman, S., Houlden, H., Holton, J. L., et al. (2018) · Brain · doi:10.1093/brain/awy157 · Cited by 74 · see citing works
Nuclear Proximity of Mtr4 to RNA Exosome Restricts DNA Mutational Asymmetry
Lim, J., Giri, P. K., Kazadi, D., Laffleur, B., Zhang, W., Grinstein, V., Pefanis, E., Brown, L. M., Ladewig, E., Martin, O. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.03.043 · Cited by 74 · see citing works
Hammack, C., Ogden, S. C., Madden, J. C., Medina, A., Xu, C., Phillips, E. O. N., Son, Y., Cone, A. S., Giovinazzi, S., Didier, R., et al. (2019) · Journal of Virology · doi:10.1128/jvi.00638-19 · Cited by 73 · see citing works
Physiological functions of programmed DNA breaks in signal-induced transcription
Puc, J., Aggarwal, A. K., & Rosenfeld, M. G. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.43 · Cited by 71 · see citing works
Activation of Oncogenic Super-Enhancers Is Coupled with DNA Repair by RAD51
Hazan, I., Monin, J., Bouwman, B. A. M., Crosetto, N., & Aqeilan, R. I. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.001 · Cited by 68 · see citing works
Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions
Campello, L., Singh, N., Advani, J., Mondal, A. K., Corso‐Díaz, X., & Swaroop, A. (2021) · Annual Review of Vision Science · doi:10.1146/annurev-vision-100419-114940 · Cited by 67 · see citing works
Highly sensitive and unbiased approach for elucidating antibody repertoires
Lin, S. G., Ba, Z., Du, Z., Zhang, Y., Hu, J., & Alt, F. W. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1608649113 · Cited by 62 · see citing works
Jacob‐Hirsch, J., Eyal, E., Knisbacher, B. A., Roth, J. F., Cesarkas, K., Dor, C., Barhom, S. F., Kunik, V., Simon, A. J., Gal, M., et al. (2018) · Cell Research · doi:10.1038/cr.2018.8 · Cited by 66 · see citing works
Ji, F., Liao, H., Pan, S. D., Ouyang, L., Jia, F., Fu, Z., Zhang, F., Geng, X., Wang, X., Li, T., et al. (2020) · Cell Research · doi:10.1038/s41422-020-0357-y · Cited by 65 · see citing works
ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses
Berger, N. D., Stanley, F. K. T., Moore, S., & Goodarzi, A. A. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0283 · Cited by 65 · see citing works
Genomic rearrangements induced by unscheduled DNA double strand breaks in somatic mammalian cells
So, A., Guen, T. L., López, B. S., & Guirouilh‐Barbat, J. (2017) · FEBS Journal · doi:10.1111/febs.14053 · Cited by 62 · see citing works
Rescue from replication stress during mitosis
Fragkos, M., & Naim, V. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1288322 · Cited by 60 · see citing works
TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription
Gómez-Herreros, F., Zagnoli-Vieira, G., Ntai, I., Martínez-Macías, M. I., Anderson, R. M., Herrero-Ruíz, A., & Caldecott, K. W. (2017) · Nature Communications · doi:10.1038/s41467-017-00307-y · Cited by 61 · see citing works
RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion are Related Processes
Lin, S. G., Ba, Z., Alt, F. W., & Zhang, Y. (2018) · Advances in immunology · doi:10.1016/bs.ai.2018.07.001 · Cited by 60 · see citing works
WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders
Aldaz, C. M., & Hussain, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238922 · Cited by 59 · see citing works
Somatic mutations in neurons during aging and neurodegeneration
Verheijen, B. M., Vermulst, M., & van Leeuwen, F. W. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1850-y · Cited by 57 · see citing works
DNA repair fidelity in stem cell maintenance, health, and disease
Mani, C., Reddy, P. H., & Palle, K. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.03.017 · Cited by 55 · see citing works
FANCD2 binding identifies conserved fragile sites at large transcribed genes in avian cells
Pentzold, C., Shah, S. A., Hansen, N. R., Tallec, B. L., Seguin‐Orlando, A., Debatisse, M., Lisby, M., & Oestergaard, V. H. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1260 · Cited by 55 · see citing works
Delaney, J. R., Patel, C. B., Bapat, J., Jones, C. M., Zapatero, M. R., Ortell, K. K., Tanios, R., Haghighiabyaneh, M., Axelrod, J. L., DeStefano, J., et al. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008558 · Cited by 55 · see citing works
Insights into the role of somatic mosaicism in the brain
Paquola, A. C. M., Erwin, J. A., & Gage, F. H. (2016) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2016.12.004 · Cited by 54 · see citing works
Bouwman, B. A. M., & Crosetto, N. (2018) · Genes · doi:10.3390/genes9120632 · Cited by 53 · see citing works
Working on Genomic Stability: From the S-Phase to Mitosis
Ovejero, S., Bueno, A., & Sacristán, M. P. (2020) · Genes · doi:10.3390/genes11020225 · Cited by 54 · see citing works
Iida, T., Iwanami, A., Sanosaka, T., Kohyama, J., Miyoshi, H., Nagoshi, N., Kashiwagi, R., Toyama, Y., Matsumoto, M., Nakamura, M., et al. (2017) · Stem Cells · doi:10.1002/stem.2581 · Cited by 53 · see citing works
DNA damage in aging, the stem cell perspective
McNeely, T., Leone, M., Yanai, H., & Beerman, I. (2020) · Human Genetics · doi:10.1007/s00439-019-02047-z · Cited by 52 · see citing works
A journey with common fragile sites: From S phase to telophase
Debatisse, M., & Rosselli, F. (2018) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22704 · Cited by 52 · see citing works
Epstein, I., & Finkbeiner, S. M. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.023 · Cited by 51 · see citing works
Watson, L. A., & Tsai, L. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2016.12.002 · Cited by 50 · see citing works
DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders
Provasek, V. E., Mitra, J., Malojirao, V. H., & Hegde, M. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094653 · Cited by 51 · see citing works
Genome Protection by DNA Polymerase θ
Wood, R. D., & Doublié, S. (2022) · Annual Review of Genetics · doi:10.1146/annurev-genet-072920-041046 · Cited by 50 · see citing works
CSMD1 regulates brain complement activity and circuit development
Baum, M. L., Wilton, D. K., Fox, R. G., Carey, A. E., Hsu, Y.-H. H., Hu, R., Jäntti, H., Fahey, J. B., Muthukumar, A. K., Salla, N., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.03.041 · Cited by 49 · see citing works
Wei, P., Lee, C., Du, Z., Schwer, B., Zhang, Y., Kao, J., Zurita, J., & Alt, F. W. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1719907115 · Cited by 46 · see citing works
Somatic mutations in the human brain: implications for psychiatric research
Nishioka, M., Bundo, M., Iwamoto, K., & Kato, T. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0129-y · Cited by 48 · see citing works
Pérez‐Rodríguez, D., Kalyva, M., Leija‐Salazar, M., Lashley, T., Tarabichi, M., Chelban, V., Gentleman, S., Schottlaender, L., Franklin, H., Vasmatzis, G., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0873-5 · Cited by 50 · see citing works
Eckelmann, B. J., Bacolla, A., Wang, H., Ye, Z., Guerrero, E. N., Jiang, W., El‐Zein, R. A., Hegde, M. L., Tomkinson, A. E., Tainer, J. A., et al. (2020) · NAR Cancer · doi:10.1093/narcan/zcaa013 · Cited by 49 · see citing works
Neuronal PAS domain proteins 1 and 3 are master regulators of neuropsychiatric risk genes
Michaelson, J. J., Shin, M.-K., Koh, J.-Y., Brueggeman, L., Zhang, A., Katzman, A., McDaniel, L., Fang, M., Pufall, M., & Pieper, A. A. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.03.021 · Cited by 47 · see citing works
The Role of Transposable Elements of the Human Genome in Neuronal Function and Pathology
Chesnokova, E., Beletskiy, A., & Kolosov, P. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105847 · Cited by 48 · see citing works
Reduced replication fork speed promotes pancreatic endocrine differentiation and controls graft size
Sui, L., Xin, Y., Du, Q., Georgieva, D., Diedenhofen, G., Haataja, L., Su, Q., Zuccaro, M. V., Kim, J., Fu, J., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.141553 · Cited by 45 · see citing works
Reid, D. A., Conlin, M. P., Yin, Y., Chang, H. H., Watanabe, G., Lieber, M. R., Ramsden, D. A., & Rothenberg, E. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1221 · Cited by 46 · see citing works
Common Fragile Sites Are Characterized by Faulty Condensin Loading after Replication Stress
Boteva, L., Nozawa, R., Naughton, C., Samejima, K., Earnshaw, W. C., & Gilbert, N. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108177 · Cited by 49 · see citing works
53BP1: Keeping It under Control, Even at a Distance from DNA Damage
Rass, E., Willaume, S., & Bertrand, P. (2022) · Genes · doi:10.3390/genes13122390 · Cited by 46 · see citing works
Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells
Moore, D. L., & Jessberger, S. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.09.007 · Cited by 45 · see citing works
Yang, X., Xu, B., Mulvey, B. B., Evans, M. K., Jordan, S., Wang, Y., Pagala, V., Peng, J., Fan, Y., Patel, A. C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0328-5 · Cited by 44 · see citing works
Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
Brambati, A., Zardoni, L., Achar, Y. J., Piccini, D., Galanti, L., Colosio, A., Foiani, M., & Liberi, G. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx945 · Cited by 43 · see citing works
WWOX, the FRA16D gene: A target of and a contributor to genomic instability
Hussain, T., Liu, B., Schrock, M. S., Williams, T. M., & Aldaz, C. M. (2018) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22693 · Cited by 43 · see citing works
DNA 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
53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice
Chen, J., Li, P., Song, L., Bai, L., Huen, M. S. Y., Liu, Y., & Lu, L. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0521-4 · Cited by 38 · see citing works
Bočkaj, I., Martini, T. E. I., Magalhães, E. S. D. C., Bakker, P. L., Boer, T. M.-D., Armandari, I., Meuleman, S. L., Mondria, M. T., Stok, C., Kok, Y. P., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009868 · Cited by 33 · see citing works
Hussain, T., Kil, H., Hattiangady, B., Lee, J., Kodali, M., Shuai, B., Attaluri, S., Takata, Y., Shen, J., Abba, M. C., et al. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.09.026 · Cited by 34 · see citing works
Cheng, Y., Snavely, A. R., Barrett, L. B., Zhang, X., Herman, C., Frost, D., Riva, P., Tochitsky, I., Kawaguchi, R., Singh, B., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109666 · Cited by 36 · see citing works
Time is ticking faster for long genes in aging
Soheili‐Nezhad, S., Ibáñez-Solé, O., Izeta, A., Hoeijmakers, J. H. J., & Stoeger, T. (2024) · Trends in Genetics · doi:10.1016/j.tig.2024.01.009 · Cited by 36 · see citing works
Keil, J. M., Doyle, D. Z., Qalieh, A., Lam, M. M. S., Funk, O. H., Qalieh, Y., Shi, L., Mohan, N., Sorel, A., & Kwan, K. Y. (2020) · Nature Communications · doi:10.1038/s41467-020-17551-4 · Cited by 33 · see citing works
Cohesin maintains replication timing to suppress DNA damage on cancer genes
Wu, J., Liu, Y., Zhangding, Z., Liu, X., Chen, A., Gan, T., Liang, H., Guo, Y., Chen, M., Liu, Y., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01458-z · Cited by 33 · see citing works
Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response
Hazan, I., Hofmann, T. G., & Aqeilan, R. I. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006436 · Cited by 31 · see citing works
DNA repair and mutations during quiescence in yeast
Gangloff, S., & Arcangioli, B. (2017) · FEMS Yeast Research · doi:10.1093/femsyr/fox002 · Cited by 33 · see citing works
Taming Tricky DSBs: ATM on duty
Clouaire, T., Marnef, A., & Legube, G. (2017) · DNA repair · doi:10.1016/j.dnarep.2017.06.010 · Cited by 32 · see citing works
Replication Stress: An Achilles' Heel of Glioma Cancer Stem–like Cells
Morgan, M. A., & Canman, C. E. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-2439 · Cited by 32 · see citing works
- Authors
- Wei, P.-C., Chang, A. N., Kao, J., Du, Z., Meyers, R. M., Alt, F. W., & Schwer, B.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Alt, Frederick W.
- Schwer, Bjoern
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 164
- Issue
- 4
- Pages
- 644-655
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4752721
- OpenAlex
- W2268858163
- Cited by
- 280
- References
- 55
- Citations by year
- 2026: 20 · 2025: 13 · 2024: 15 · 2023: 23 · 2022: 24 · 2021: 32 · 2020: 31 · 2019: 20 · 2018: 37 · 2017: 40 · 2016: 25
- FWCI
- 21.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (K01AG043630)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- neural stem/progenitor cells, DNA double-strand breaks, non-homologous end joining, replication stress, synaptic function, neuronal adhesion, tumor suppression genes, mental illness, brain development
- MeSH terms
- Animals, Brain, Cell Adhesion, DNA Repair, Humans, Nerve Tissue Proteins, Synapses, Transcription Factors, Translocation, Genetic, Cell Adhesion Molecules, Neuronal, Aphidicolin, Genome, Mice, Basic Helix-Loop-Helix Proteins, DNA Breaks, GPI-Linked Proteins, Neural Stem Cells, DNA End-Joining Repair
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
