The core spliceosome as target and effector of non-canonical ATM signalling
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In response to DNA damage, tissue homoeostasis is ensured by protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage response signalling pathways coordinate these processes, partly by propagating gene-expression-modulating signals. DNA damage influences not only the abundance of messenger RNAs, but also their coding information through alternative splicing. Here we show that transcription-blocking DNA lesions promote chromatin displacement of late-stage spliceosomes and initiate a positive feedback loop centred on the signalling kinase ATM. We propose that initial spliceosome displacement and subsequent R-loop formation is triggered by pausing of RNA polymerase at DNA lesions. In turn, R-loops activate ATM, which signals to impede spliceosome organization further and augment ultraviolet-irradiation-triggered alternative splicing at the genome-wide level. Our findings define R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells, and highlight a key role for spliceosome displacement in this process.
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If replication forks or transcription complexes encounter polymerase-blocking lesions, this can lead to formation of a DSB or R-loop, which potently activate signaling events that halt cell cycle progression and promote repair.
“If replication forks or transcription complexes encounter polymerase-blocking lesions (Vermeij et al., 2016), this can lead to the formation of a DSB or R-loop (Tresini et al., 2015), which potently activate signaling events that halt cell cycle progression and promote repair.”
From DNA damage-how and why we age? (2021) · cites this paper as Tresini et al., 2015
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1 retracted
KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling
Kaidi, A., & Jackson, S. P. (2013) · Nature · doi:10.1038/nature12201 · Cited by 167 · see citing works
RetractedCox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
The DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368 · see citing works
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466 · see citing works
ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage
Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., et al. (2007) · Science · doi:10.1126/science.1140321 · Cited by 3,075 · see citing works
Hoeijmakers, J. H. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804615 · Cited by 2,239 · see citing works
Self-citationThe ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Shiloh, Y., & Ziv, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3546 · Cited by 1,649 · see citing works
ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex
Lee, J.-H., & Paull, T. T. (2005) · Science · doi:10.1126/science.1108297 · Cited by 1,424 · see citing works
Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Matsuoka, S. (1998) · Science · doi:10.1126/science.282.5395.1893 · Cited by 1,322 · see citing works
R Loops: From Transcription Byproducts to Threats to Genome Stability
Aguilera, A., & García‐Muse, T. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.009 · Cited by 1,029 · see citing works
Alternative splicing: a pivotal step between eukaryotic transcription and translation
Kornblihtt, A. R., Schor, I. E., Alló, M., Dujardin, G., Petrillo, E., & Muñoz, M. J. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3525 · Cited by 851 · see citing works
Ribonuclease H: the enzymes in eukaryotes
Cerritelli, S. M., & Crouch, R. J. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06908.x · Cited by 816 · see citing works
Huertas, P., & Aguilera, A. (2003) · Molecular Cell · doi:10.1016/j.molcel.2003.08.010 · Cited by 750 · see citing works
Splicing factor SF3b as a target of the antitumor natural product pladienolide
Kotake, Y., Sagane, K., Owa, T., Mimori‐Kiyosue, Y., Shimizu, H., Uesugi, M., Ishihama, Y., Iwata, M., & Mizui, Y. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.16 · Cited by 648 · see citing works
BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2
Bhatia, V., Barroso, S. I., García-Rubio, M. L., Tumini, E., Herrera‐Moyano, E., & Aguilera, A. (2014) · Nature · doi:10.1038/nature13374 · Cited by 527 · see citing works
Reijns, M. A. M., Rabe, B., Rigby, R. E., Mill, P., Astell, K. R., Lettice, L. A., Boyle, S., Leitch, A., Keighren, M., Kilanowski, F., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.011 · Cited by 466 · see citing works
Shen, S., Park, J. W., Huang, J., Dittmar, K. A., Lu, Z., Zhou, Q., Carstens, R. P., & Xing, Y. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr1291 · Cited by 362 · see citing works
DNA Damage Regulates Alternative Splicing through Inhibition of RNA Polymerase II Elongation
Muñoz, M. J., Perez-Santángelo, S., Paronetto, M. P., de la Mata, M., Pelisch, F., Boireau, S., Glover-Cutter, K. M., Ben-Dov, C., Blaustein, M., Lozano, J. J., et al. (2009) · Cell · doi:10.1016/j.cell.2009.03.010 · Cited by 310 · see citing works
UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair
Schwertman, P., Lagarou, A., Dekkers, D. H. W., Raams, A., van der Hoek, A. C., Laffeber, C., Hoeijmakers, J. H. J., Demmers, J. A. A., Fousteri, M., Vermeulen, W., et al. (2012) · Nature Genetics · doi:10.1038/ng.2230 · Cited by 279 · see citing works
Self-citationDNA Damage Response: Three Levels of DNA Repair Regulation
Sirbu, B. M., & Cortez, D. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012724 · Cited by 272 · see citing works
RNA structure and the mechanisms of alternative splicing
McManus, C. J., & Graveley, B. R. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.04.001 · Cited by 269 · 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
The spliceosome: a flexible, reversible macromolecular machine
Hoskins, A. A., & Moore, M. J. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.02.009 · Cited by 236 · see citing works
Wuarin, J., & Schibler, U. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.11.7219 · Cited by 233 · see citing works
Hanasoge, S., & Ljungman, M. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm157 · Cited by 216 · see citing works
Zhou, H.-L., Luo, G., Wise, J. A., & Lou, H. J. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt875 · Cited by 201 · see citing works
Mammalian Transcription-Coupled Excision Repair
Vermeulen, W., & Fousteri, M. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012625 · Cited by 184 · see citing works
Self-citationThe Ewing Sarcoma Protein Regulates DNA Damage-Induced Alternative Splicing
Paronetto, M. P., Miñana, B., & Valcárcel, J. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.05.035 · Cited by 175 · see citing works
Houtsmuller, A. B., & Vermeulen, W. (2000) · Histochemistry and Cell Biology · doi:10.1007/s004180000234 · Cited by 173 · see citing works
Self-citationActivation of multiple DNA repair pathways by sub-nuclear damage induction methods
Dinant, C., de Jager, M., Essers, J., van Cappellen, W. A., Kanaar, R., Houtsmuller, A. B., & Vermeulen, W. (2007) · Journal of Cell Science · doi:10.1242/jcs.004523 · Cited by 165 · see citing works
Self-citationCotranscriptional exon skipping in the genotoxic stress response
Dutertre, M., Sanchez, G., Cian, M. D., Barbier, J., Dardenne, É., Gratadou, L., Dujardin, G., Jossic-Corcos, C. L., Corcos, L., & Auboeuf, D. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1912 · Cited by 161 · see citing works
SON Controls Cell-Cycle Progression by Coordinated Regulation of RNA Splicing
Ahn, E.-Y., DeKelver, R. C., Lo, M., Nguyen, T. A. T., Matsuura, S., Boyapati, A., Pandit, S., Fu, X., & Zhang, D. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.03.014 · Cited by 160 · see citing works
A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1
Blasius, M., Forment, J. V., Thakkar, N. P., Wagner, S., Choudhary, C., & Jackson, S. P. (2011) · Genome biology · doi:10.1186/gb-2011-12-8-r78 · Cited by 155 · see citing works
DNA damage response and transcription
Lagerwerf, S., Vrouwe, M. G., Overmeer, R., Fousteri, M. I., & Mullenders, L. H. F. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.04.024 · Cited by 153 · see citing works
Self-citationThe neurological phenotype of ataxia-telangiectasia: Solving a persistent puzzle
Biton, S., Barzilai, A., & Shiloh, Y. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.03.006 · Cited by 133 · see citing works
Wuarin, J., & Schibler, U. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.11.7219-7225.1994 · Cited by 117 · see citing works
Galiveti, C. R., Rozhdestvensky, T. S., Brosius, J., Lehrach, H. R., & Konthur, Z. (2009) · RNA · doi:10.1261/rna.1755810 · Cited by 104 · see citing works
Dutertre, M., Sanchez, G., Barbier, J., Corcos, L., & Auboeuf, D. (2011) · RNA Biology · doi:10.4161/rna.8.5.16016 · Cited by 102 · see citing works
Investigating the Structure of Human RNase H1 by Site-directed Mutagenesis
Wu, H., Lima, W. F., & Crooke, S. T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009676200 · Cited by 90 · see citing works
The spliceosomal proteome: At the heart of the largest cellular ribonucleoprotein machine
Valadkhan, S., & Jaladat, Y. (2010) · PROTEOMICS · doi:10.1002/pmic.201000354 · Cited by 86 · see citing works
Nakazawa, Y., Yamashita, S., Lehmann, A. R., & Ogi, T. (2010) · DNA repair · doi:10.1016/j.dnarep.2010.01.015 · Cited by 85 · see citing works
A Stochastic View of Spliceosome Assembly and Recycling in the Nucleus
Rino, J., Carvalho, T., Braga, J., Desterro, J. M. P., Lührmann, R., & Carmo‐Fonseca, M. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030201 · Cited by 61 · see citing works
Coupling Between Transcription and Alternative Splicing
Schor, I. E., Acuña, L. I. G., & Kornblihtt, A. R. (2013) · Cancer treatment and research · doi:10.1007/978-3-642-31659-3_1 · Cited by 51 · see citing works
RNA Splicing: A New Player in the DNA Damage Response
Lenzken, S. C., Loffreda, A., & Barabino, S. M. L. (2013) · International Journal of Cell Biology · doi:10.1155/2013/153634 · Cited by 46 · see citing works
Cross-talk in transcription, splicing and chromatin: who makes the first call?
Alexander, R. D., & Beggs, J. D. (2010) · Biochemical Society Transactions · doi:10.1042/bst0381251 · Cited by 43 · see citing works
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ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response
Blackford, A. N., & Jackson, S. P. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.015 · Cited by 1,953 · see citing works
R loops: new modulators of genome dynamics and function
Santos-Pereira, J. M., & Aguilera, A. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3961 · Cited by 752 · see citing works
R-Loops as Cellular Regulators and Genomic Threats
Crossley, M. P., Bocek, M. J., & Cimprich, K. A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.024 · Cited by 732 · see citing works
RNA splicing factors as oncoproteins and tumour suppressors
Dvinge, H., Kim, E. H., Abdel-Wahab, O. I., & Bradley, R. K. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.51 · Cited by 684 · see citing works
Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Kotsantis, P., Petermann, E., & Boulton, S. J. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1461 · Cited by 416 · see citing works
DNA damage-how and why we age?
Yousefzadeh, M., Henpita, C., Vyas, R., Soto-Palma, C., Robbins, P., & Niedernhofer, L. (2021) · eLife · doi:10.7554/elife.62852 · Cited by 399 · see citing works
Chen, L., Chen, J., Zhang, X., Gu, Y., Xiao, R., Shao, C., Tang, P., Qian, H., Luo, D., Li, H., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.008 · Cited by 373 · see citing works
The Fanconi Anemia Pathway Maintains Genome Stability by Coordinating Replication and Transcription
Schwab, R. A., Nieminuszczy, J., Shah, F., Langton, J., Martínez, D. L., Liang, C., Cohn, M. A., Gibbons, R. J., Deans, A. J., & Niedźwiedź, W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.012 · Cited by 356 · see citing works
The DNA damage response to transcription stress
Lans, H., Hoeijmakers, J. H. J., Vermeulen, W., & Marteijn, J. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0169-4 · Cited by 321 · see citing works
Self-citationChen, L., Chen, J., Huang, Y.-J., Gu, Y., Qiu, J., Qian, H., Shao, C., Zhang, X., Hu, J., Li, H., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2017.12.029 · Cited by 295 · see citing works
Cellular functions of the protein kinase ATM and their relevance to human disease
Lee, J., & Paull, T. T. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00394-2 · Cited by 290 · see citing works
ATM and ATR signaling at a glance
Awasthi, P., Foiani, M., & Kumar, A. (2015) · Journal of Cell Science · doi:10.1242/jcs.169730 · Cited by 277 · see citing works
Chromosome instability syndromes
Taylor, A. M. R., Rothblum‐Oviatt, C., Ellis, N. A., Hickson, I. D., Meyer, S., Crawford, T. O., Smogorzewska, A., Pietrucha, B. M., Weemaes, C. M. R., & Stewart, G. S. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0113-0 · Cited by 227 · see citing works
Defective control of pre–messenger RNA splicing in human disease
Chabot, B., & Shkreta, L. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201510032 · Cited by 209 · see citing works
Tumour predisposition and cancer syndromes as models to study gene–environment interactions
Carbone, M., Arron, S. T., Beutler, B., Bononi, A., Cavenee, W. K., Cleaver, J. E., Croce, C. M., D’Andrea, A. D., Foulkes, W. D., Gaudino, G., et al. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0265-y · Cited by 195 · see citing works
C9orf72 expansion disrupts ATM-mediated chromosomal break repair
Walker, C., Herranz-Martín, S., Karyka, E., Liao, C., Lewis, K. E. A., Elsayed, W., Lukashchuk, V., Chiang, S., Ray, S., Mulcahy, P. J., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4604 · Cited by 181 · see citing works
Transcription as a Threat to Genome Integrity
Gaillard, H., & Aguilera, A. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014908 · Cited by 173 · 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
Epigenome Maintenance in Response to DNA Damage
Dabin, J., Fortuny, A., & Polo, S. E. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.006 · Cited by 161 · see citing works
Genome integrity and disease prevention in the nervous systemPreprint
McKinnon, P. J. (2017) · Genes & Development · doi:10.1101/gad.301325.117 · Cited by 155 · see citing works
R-loop generation during transcription: Formation, processing and cellular outcomes
Belotserkovskii, B. P., Tornaletti, S., D’Souza, A. D., & Hanawalt, P. C. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.08.009 · Cited by 155 · see citing works
ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor
Lavin, M. F., Kozlov, S., Gatei, M. H., & Kijas, A. W. (2015) · Biomolecules · doi:10.3390/biom5042877 · Cited by 152 · see citing works
The RNA Splicing Response to DNA Damage
Shkreta, L., & Chabot, B. (2015) · Biomolecules · doi:10.3390/biom5042935 · Cited by 154 · see citing works
Roles of UVA radiation and DNA damage responses in melanoma pathogenesis
Khan, A. Q., Travers, J. B., & Kemp, M. G. (2018) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22176 · Cited by 152 · see citing works
The Cellular Response to Transcription-Blocking DNA Damage
Gregersen, L. H., & Svejstrup, J. Q. (2018) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.02.010 · Cited by 145 · see citing works
Genome-wide RNA polymerase stalling shapes the transcriptome during aging
Gyenis, Á., Chang, J., Demmers, J. J. P. G., Bruens, S. T., Barnhoorn, S., Brandt, R. M. C., Baar, M. P., Rašeta, M., Derks, K., Hoeijmakers, J. H. J., et al. (2023) · Nature Genetics · doi:10.1038/s41588-022-01279-6 · Cited by 140 · see citing works
Self-citationSplicing factor gene mutations in hematologic malignancies
Sáez, B., Walter, M. J., & Graubert, T. A. (2016) · Blood · doi:10.1182/blood-2016-10-692400 · Cited by 130 · see citing works
Targeting DNA repair pathway in cancer: Mechanisms and clinical application
Wang, M., Chen, S., & Ao, D. (2021) · MedComm · doi:10.1002/mco2.103 · Cited by 134 · see citing works
XRN2 Links Transcription Termination to DNA Damage and Replication Stress
Morales, J. C., Richard, P., Patidar, P. L., Motea, E. A., Dang, T. T., Manley, J. L., & Boothman, D. A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006107 · Cited by 126 · see citing works
R-loops: formation, function, and relevance to cell stress
Allison, D. F., & Wang, G. G. (2019) · Cell Stress · doi:10.15698/cst2019.02.175 · Cited by 122 · see citing works
RECQ-like helicases Sgs1 and BLM regulate R-loop–associated genome instability
Chang, E. Y., Novoa, C. A., Aristizabal, M. J., Coulombe, Y., Segovia, R., Chaturvedi, R., Shen, Y., Keong, C., Tam, A., Jones, S. J. M., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201703168 · Cited by 120 · see citing works
ATM directs DNA damage responses and proteostasis via genetically separable pathways
Lee, J., Mand, M. R., Kao, C.-H., Zhou, Y., Ryu, S. W., Richards, A., Coon, J. J., & Paull, T. T. (2018) · Science Signaling · doi:10.1126/scisignal.aan5598 · Cited by 118 · see citing works
Moreno, N. N., Olthof, A. M., & Svejstrup, J. Q. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052621-091205 · Cited by 115 · see citing works
Sridhara, S. R. C., Carvalho, S., Grosso, A. R., Gallego-Paez, L. M., Carmo‐Fonseca, M., & de Almeida, S. F. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.050 · Cited by 116 · see citing works
RNA Processing and Genome Stability: Cause and Consequence
Wickramasinghe, V. O., & Venkitaraman, A. R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.001 · Cited by 107 · see citing works
Directing the use of DDR kinase inhibitors in cancer treatment
Brandsma, I., Fleuren, E. D. G., Williamson, C. T., & Lord, C. J. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1389895 · Cited by 107 · see citing works
Quin, J. E., Chan, K. T., Devlin, J. R., Cameron, D. P., Diesch, J., Cullinane, C. M., Ahern, J., Khot, A. S., Hein, N., George, A. J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10452 · Cited by 102 · see citing works
Deciphering UV‐induced DNA Damage Responses to Prevent and Treat Skin Cancer
Lee, J. W., Ratnakumar, K., Hung, K., Rokunohe, D., & Kawasumi, M. (2020) · Photochemistry and Photobiology · doi:10.1111/php.13245 · Cited by 112 · see citing works
Phan, L. M., & Rezaeian, A.-H. (2021) · Genes · doi:10.3390/genes12060845 · Cited by 105 · see citing works
Mutually exclusive acetylation and ubiquitylation of the splicing factor SRSF5 control tumor growth
Chen, Y., Huang, Q., Liu, W., Zhu, Q., Cui, C., Xu, L., Guo, X. L., Wang, P., Liu, J., Dong, G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04815-3 · Cited by 99 · see citing works
Destabilization of linker histone H1.2 is essential for ATM activation and DNA damage repair
Li, Z., Li, Y., Tang, M., Peng, B., Lu, X., Yang, Q., Zhu, Q., Hou, T., Li, M., Liu, C., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0048-0 · Cited by 99 · see citing works
Efficient Pre-mRNA Cleavage Prevents Replication-Stress-Associated Genome Instability
Teloni, F., Michelena, J., Lezaja, A., Kilic, S., Ambrosi, C. M., Menon, S., Dobrovolná, J., Imhof, R., Janščák, P., Baubec, T., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.11.036 · Cited by 97 · see citing works
CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1
Hluchý, M., Gajdušková, P., Mozos, I. R. D. L., Rájecký, M., Kluge, M., Berger, B., Slabá, Z., Potěšil, D., Weiß, E., Ule, J., et al. (2022) · Nature · doi:10.1038/s41586-022-05204-z · Cited by 96 · see citing works
RTEL1 suppresses G-quadruplex-associated R-loops at difficult-to-replicate loci in the human genome
Wu, W., Bhowmick, R., Vogel, I., Özer, Ö., Ghisays, F., Thakur, R. S., León, E., Richter, P. H., Ren, L., Petrini, J. H. J., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0408-6 · Cited by 92 · see citing works
Efficient RNA polymerase II pause release requires U2 snRNP function
Caizzi, L., Monteiro-Martins, S., Schwalb, B., Lysakovskaia, K., Schmitzová, J., Sawicka, A., Chen, Y., Lidschreiber, M., & Cramer, P. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.02.016 · Cited by 96 · see citing works
Sensing R-Loop-Associated DNA Damage to Safeguard Genome Stability
Rinaldi, C., Pizzul, P., Longhese, M. P., & Bonetti, D. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.618157 · Cited by 91 · see citing works
Awwad, S. W., Abu‐Zhayia, E. R., Guttmann‐Raviv, N., & Ayoub, N. (2017) · EMBO Reports · doi:10.15252/embr.201643191 · Cited by 85 · see citing works
Lavigne, M. D., Konstantopoulos, D., Ntakou‐Zamplara, K. Z., Liakos, A., & Fousteri, M. I. (2017) · Nature Communications · doi:10.1038/s41467-017-02145-4 · Cited by 83 · see citing works
Pharmacology of Modulators of Alternative Splicing
Bates, D. O., Morris, J. C., Oltean, S., & Donaldson, L. F. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011239 · Cited by 81 · see citing works
ATM pathway activation limits R-loop-associated genomic instability in Werner syndrome cells
Marabitti, V., Lillo, G., Malacaria, E., Palermo, V., Sanchez, M., Pichierri, P., & Franchitto, A. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz025 · Cited by 79 · see citing works
R-ChIP for genome-wide mapping of R-loops by using catalytically inactive RNASEH1
Chen, J., Zhang, X., Fu, X., & Chen, L. (2019) · Nature Protocols · doi:10.1038/s41596-019-0154-6 · Cited by 81 · see citing works
Lee, J., & Paull, T. T. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101511 · Cited by 79 · see citing works
p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage
Borisova, M. E., Voigt, A., Tollenaere, M. A. X., Sahu, S. K., Juretschke, T., Kreim, N., Mailand, N., Choudhary, C., Bekker‐Jensen, S., Akutsu, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03417-3 · Cited by 82 · see citing works
Carrocci, T. J., Zoerner, D. M., Paulson, J. C., & Hoskins, A. A. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1349 · Cited by 72 · see citing works
The MYC mRNA 3′‐UTR couples RNA polymerase II function to glutamine and ribonucleotide levels
Dejure, F. R., Royla, N., Herold, S., Kalb, J., Walz, S., Ade, C. P., Mastrobuoni, G., Vanselow, J. T., Schlösser, A., Wolf, E., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796662 · Cited by 69 · see citing works
Human ribonuclease H1 resolves R-loops and thereby enables progression of the DNA replication fork
Parajuli, S. P., Teasley, D. C., Murali, B., Jackson, J., Vindigni, A., & Stewart, S. A. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.787473 · Cited by 71 · see citing works
Splicing alterations in healthy aging and disease
Angarola, B. L., & Anczuków, O. (2021) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1643 · Cited by 69 · see citing works
Steurer, B., Janssens, R. C., Geijer, M. E., Aprile-Garcia, F., Geverts, B., Theil, A. F., Hummel, B., van Royen, M. E., Evers, B., Bernards, R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31329-w · Cited by 65 · see citing works
Self-citationBon voyage: A transcriptional journey around DNA breaks
Caron, P., van der Linden, J., & van Attikum, H. (2019) · DNA repair · doi:10.1016/j.dnarep.2019.102686 · Cited by 64 · see citing works
The dark side of RNA:DNA hybrids
Brambati, A., Zardoni, L., Nardini, E., Pellicioli, A., & Liberi, G. (2020) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2020.108300 · Cited by 65 · see citing works
Canonical DNA Repair Pathways Influence R-Loop-Driven Genome Instability
Stirling, P. C., & Hieter, P. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.07.014 · Cited by 59 · see citing works
Geijer, M. E., & Marteijn, J. A. F. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.08.007 · Cited by 60 · see citing works
Self-citationTanikawa, M., Sanjiv, K., Helleday, T., Herr, P., & Mortusewicz, O. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.70 · Cited by 59 · see citing works
The RNA Response to DNA Damage
Giono, L. E., Moreno, N. N., Botto, A. E. C., Dujardin, G., Muñoz, M. J., & Kornblihtt, A. R. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.03.004 · Cited by 59 · see citing works
Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role
Shen, S.-M., Ji, Y., Zhang, C., Dong, S.-S., Yang, S., Xiong, Z., Ge, M.-K., Yu, Y., Li, X., Guo, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04760-1 · Cited by 59 · see citing works
Historical perspective on the DNA damage response
Hanawalt, P. C. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.10.001 · Cited by 57 · see citing works
RNA: a double-edged sword in genome maintenance
Zong, D., Oberdoerffer, P., Batista, P. J., & Nussenzweig, A. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0263-7 · Cited by 57 · see citing works
Burger, K., Ketley, R. F., & Gullerová, M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00061 · Cited by 56 · see citing works
Majora, M., Sondenheimer, K., Knechten, M., Uthe, I., Esser, C., Schiavi, A., Ventura, N., & Krutmann, J. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aam7510 · Cited by 56 · see citing works
Cristini, A., Park, J.-H., Capranico, G., Legube, G., Favre, G., & Sordet, O. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1196 · Cited by 55 · see citing works
Sarkar, K., Han, S., Wen, K., Ochs, H. D., Dupré, L., Seidman, M. M., & Vyas, Y. M. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.11.023 · Cited by 55 · see citing works
Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency
Reid-Bayliss, K. S., Arron, S. T., Loeb, L. A., Bezrookove, V., & Cleaver, J. E. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610020113 · Cited by 55 · see citing works
The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing
Goulielmaki, E., Tsekrekou, M., Batsiotos, N., Ascensão-Ferreira, M., Ledaki, E., Stratigi, K., Chatzinikolaou, G., Topalis, P., Kosteas, T., Altmüller, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23505-1 · Cited by 54 · see citing works
Self-citationR-Loops in Genome Instability and Cancer
Li, F., Zafar, A., Luo, L., Denning, A. M., Gu, J., Bennett, A., Yuan, F., & Zhang, Y. (2023) · Cancers · doi:10.3390/cancers15204986 · Cited by 54 · see citing works
Jia, N., Guo, C., Nakazawa, Y., van den Heuvel, D., Luijsterburg, M. S., & Ogi, T. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103192 · Cited by 50 · see citing works
DNA damage mediated transcription arrest: Step back to go forward
Mullenders, L. H. F. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.09.005 · Cited by 51 · see citing works
Self-citationNascent-protein ubiquitination is required for heat shock–induced gene downregulation in human cells
Aprile-Garcia, F., Tomar, P., Hummel, B., Khavaran, A., & Sawarkar, R. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0182-x · Cited by 51 · see citing works
Multilayered Reprogramming in Response to Persistent DNA Damage in C. elegans
Edifizi, D., Nolte, H., Babu, V. V. S., Castells‐Roca, L., Mueller, M. M., Brodesser, S., Krüger, M., & Schumacher, B. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.028 · Cited by 50 · see citing works
Clinical potential of ATM inhibitors
Lavin, M. F., & Yeo, A. J. (2020) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2020.111695 · Cited by 49 · see citing works
Oxidative stress and the multifaceted roles of ATM in maintaining cellular redox homeostasis
Lee, J. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103269 · Cited by 50 · see citing works
Su, C., Zhao, H., Zhao, Y., Ji, H., Wang, Y., Zhi, L., & Li, X. (2017) · Scientific Reports · doi:10.1038/srep43897 · Cited by 49 · see citing works
Replication protein A binds RNA and promotes R-loop formation
Mazina, O. M., Somarowthu, S., Kadyrova, L. Y., Baranovskiy, A. G., Tahirov, T. H., Kadyrov, F. A., & Mazin, A. V. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013812 · Cited by 49 · see citing works
Poly-ADP-ribosylation drives loss of protein homeostasis in ATM and Mre11 deficiency
Lee, J., Ryu, S. W., Ender, N. A., & Paull, T. T. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.01.019 · Cited by 49 · see citing works
García-Benítez, F., Gaillard, H., & Aguilera, A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707845114 · Cited by 47 · see citing works
The cerebellar degeneration in ataxia-telangiectasia: A case for genome instability
Shiloh, Y. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102950 · Cited by 47 · see citing works
Muñoz, M. J., Moreno, N. N., Giono, L. E., Botto, A. E. C., Dujardin, G., Bastianello, G., Lavore, S., Torres-Méndez, A., Menck, C. F. M., Blencowe, B. J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.066 · Cited by 45 · see citing works
Aquarius is required for proper CtIP expression and homologous recombination repair
Sakasai, R., Isono, M., Wakasugi, M., HASHIMOTO, M. W., Sunatani, Y., Matsui, T., Shibata, A., Matsunaga, T., & Iwabuchi, K. (2017) · Scientific Reports · doi:10.1038/s41598-017-13695-4 · Cited by 45 · see citing works
Non-canonical functions of spliceosome components in cancer progression
Ivanova, O. M., Anufrieva, K. S., Kazakova, A. N., Malyants, I. K., Shnaider, P. V., Lukina, M. M., & Shender, V. О. (2023) · Cell Death and Disease · doi:10.1038/s41419-022-05470-9 · Cited by 44 · see citing works
Local endothelial DNA repair deficiency causes aging-resembling endothelial-specific dysfunction
Bautista‐Niño, P. K., Portilla-Fernández, E., Rubio‐Beltrán, E., van der Linden, J., VRIES, R. D., van Veghel, R., de Boer, M., Durik, M., Ridwan, Y. R., Brandt, R. M. C., et al. (2020) · Clinical Science · doi:10.1042/cs20190124 · Cited by 44 · see citing works
Self-citationHypoxia-induced SETX links replication stress with the unfolded protein response
Ramachandran, S., Ma, T. S., Griffin, J., Ng, N., Foskolou, I. P., Hwang, M., Victori, P., Cheng, W., Buffa, F. M., Leszczyńska, K. B., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24066-z · Cited by 44 · see citing works
Lee, J. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102808 · Cited by 46 · see citing works
Dutertre, M., & Vagner, S. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.09.019 · Cited by 43 · see citing works
FACT subunit Spt16 controls UVSSA recruitment to lesion-stalled RNA Pol II and stimulates TC-NER
Wienholz, F., Zhou, D., der Velden, Y. T.-V., Schwertman, P., Tresini, M., Pines, A., van Toorn, M., Bezstarosti, K., Demmers, J., & Marteijn, J. A. F. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz055 · Cited by 41 · see citing works
Self-citationReplication Fork Protection Factors Controlling R-Loop Bypass and Suppression
Chang, E., & Stirling, P. C. (2017) · Genes · doi:10.3390/genes8010033 · Cited by 40 · see citing works
Anufrieva, K. S., Shender, V. О., Arapidi, G. P., Pavlyukov, M. S., Shakhparonov, M. I., Shnaider, P. V., Butenko, I., Lagarkova, M. A., & Govorun, V. M. (2018) · Genome Medicine · doi:10.1186/s13073-018-0557-y · Cited by 40 · see citing works
R-loops’ m6A modification and its roles in cancers
Qiu, Y., Man, C., Zhu, L., Zhang, S., Wang, X., Gong, D., & Fan, Y. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02148-y · Cited by 39 · see citing works
Walker, C., & El‐Khamisy, S. F. (2018) · Brain · doi:10.1093/brain/awy076 · Cited by 39 · see citing works
Chakraborty, A., Tapryal, N., Venkova, T., Mitra, J., Vasquez, V., Sarker, A. H., Duarte‐Silva, S., Huai, W., Ashizawa, T., Ghosh, G., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917280117 · Cited by 38 · see citing works
RNase H1, the Gold Standard for R-Loop Detection
Cerritelli, S. M., Sakhuja, K., & Crouch, R. J. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2477-7_7 · Cited by 39 · see citing works
hPso4/hPrp19: a critical component of DNA repair and DNA damage checkpoint complexes
Mahajan, K. N. (2015) · Oncogene · doi:10.1038/onc.2015.321 · Cited by 34 · see citing works
- Authors
- Tresini, M., Warmerdam, D. O., Kolovos, P., Snijder, L., Vrouwe, M. G., Demmers, J. A. A., van IJcken, W. F. J., Grosveld, F. G., Medema, R. H., Hoeijmakers, J. H. J., Mullenders, L. H. F., Vermeulen, W., & Marteijn, J. A.
- Affiliations
- Erasmus MC (NL)
- The Netherlands Cancer Institute (NL)
- Leiden University Medical Center (NL)
- Corresponding author
- Tresini, Maria
- Vermeulen, Wim
- Marteijn, Jurgen A.
- ORCID
- Venue
- Nature
- Published
- 2015-06-24
- Volume
- 523
- Issue
- 7558
- Pages
- 53-58
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4501432
- OpenAlex
- W1823908009
- Cited by
- 252
- References
- 45
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 22 · 2023: 21 · 2022: 22 · 2021: 20 · 2020: 24 · 2019: 25 · 2018: 27 · 2017: 31 · 2016: 25 · 2015: 14
- FWCI
- 14.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- ZonMw (912.12.132, 912.08.031, 854.11.002)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (935.11.042, 823.02.013, 854.11.002, 912.12.132, 912.08.031)
- National Institute on Aging (P01AG017242)
- FP7 Ideas: European Research Council (340988, 233424)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- 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
- ATM kinase, alternative splicing, DNA damage response, R-loops, U2 snRNP, U5 snRNP, UV irradiation, RNA polymerase pausing, feed-forward loop, nascent RNA
- MeSH terms
- Cell Line, Chromatin, DNA Damage, Enzyme Activation, Humans, DNA-Directed RNA Polymerases, Ultraviolet Rays, Signal Transduction, Spliceosomes, Alternative Splicing, Ataxia Telangiectasia Mutated Proteins
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