Chromosomal Translocations in Human Cells Are Generated by Canonical Nonhomologous End-Joining
Open accessAbstract
Breakpoint junctions of the chromosomal translocations that occur in human cancers display hallmarks of nonhomologous end-joining (NHEJ). In mouse cells, translocations are suppressed by canonical NHEJ (c-NHEJ) components, which include DNA ligase IV (LIG4), and instead arise from alternative NHEJ (alt-NHEJ). Here we used designer nucleases (ZFNs, TALENs, and CRISPR/Cas9) to introduce DSBs on two chromosomes to study translocation joining mechanisms in human cells. Remarkably, translocations were altered in cells deficient for LIG4 or its interacting protein XRCC4. Translocation junctions had significantly longer deletions and more microhomology, indicative of alt-NHEJ. Thus, unlike mouse cells, translocations in human cells are generated by c-NHEJ. Human cancer translocations induced by paired Cas9 nicks also showed a dependence on c-NHEJ, despite having distinct joining characteristics. These results demonstrate an unexpected and striking species-specific difference for common genomic rearrangements associated with tumorigenesis.
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Paired nicking by a Cas9 nickase at two target sites on opposite strands can significantly increase target specificity because off-target single nicks are faithfully repaired.
“form of Cas9 that generates single-stranded break rather than DSB) to generate paired nicks on the two strands of target sequence can significantly increase target specificity because off-target single nicks are faithfully repaired.51”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [51]
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Cites
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Ku80-deficient Cells Exhibit Excess Degradation of Extrachromosomal DNA
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BackgroundSelf-citationFormation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70
Weinstock, D. M., Brunet, E., & Jasin, M. (2007) · Nature Cell Biology · doi:10.1038/ncb1624 · Cited by 167 · cited 2× · see citing works
“…performed in mouse cells, in particular in lymphoid cells involving programmed double-stranded breaks (DSBs) and in embryonic stem cells using I-SceI or zinc finger nuclease (ZFN)-generated DSBs (Boboila et al., 2012; Nussenzweig and Nussenzweig, 2010; Weinstock et al., 2007; Simsek et al., 2011).”
BackgroundSelf-citationKu86 represses lethal telomere deletion events in human somatic cells
Wang, Y., Ghosh, G., & Hendrickson, E. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903362106 · Cited by 164 · cited 2× · see citing works
“, 2002) due to an essential role in telomere maintenance (Wang et al., 2009), whereas rodent cells and mice are viable in the absence of Ku (Nussenzweig et al.”
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“Loss of c-NHEJ components does not, however, completely abrogate NHEJ (Delacôte et al., 2002; Kabotyanski et al., 1998; Liang and Jasin, 1996), suggesting that there are alternative ways to join ends, referred to as alt-NHEJ.”
BackgroundCancer translocations in human cells induced by zinc finger and TALE nucleasesPreprint
Piganeau, M., Ghezraoui, H., Cian, A. D., Guittat, L., Tomishima, M. J., Perrouault, L., René, O., Katibah, G. E., Zhang, L., Holmes, M. C., et al. (2013) · Genome Research · doi:10.1101/gr.147314.112 · Cited by 147 · cited 14× · see citing works
“Similarly, cancer and model translocations induced by nucleases in several human cell lines also show little or no microhomology at translocation junctions (Brunet et al., 2009; Piganeau et al., 2013).”
BackgroundMethodInfluentialSelf-citationReplicative mechanisms for CNV formation are error prone
Carvalho, C. M. B., Pehli̇van, D., Ramocki, M. B., Fang, P., Alleva, B., Franco, L. M., Belmont, J. W., Hastings, P. J., & Lupski, J. R. (2013) · Nature Genetics · doi:10.1038/ng.2768 · Cited by 144 · cited 2× · see citing works
“…has similarities to what has been termed microhomology-mediated break-induced replication, which has been postulated as a lar Cell 55, 829–842, September 18, 2014 ª2014 Elsevier Inc. 839 mechanism to give rise to copy number variants in the germline (Carvalho et al., 2013; Hastings et al., 2009).”
BackgroundTriggers for genomic rearrangements: insights into genomic, cellular and environmental influences
Mani, R. S., & Chinnaiyan, A. M. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2883 · Cited by 142 · cited 1× · see citing works
“Recurrent reciprocal chromosomal translocations are associated with oncogenesis (Mani and Chinnaiyan, 2010; Mitelman et al., 2007).”
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“…performed in mouse cells, in particular in lymphoid cells involving programmed double-stranded breaks (DSBs) and in embryonic stem cells using I-SceI or zinc finger nuclease (ZFN)-generated DSBs (Boboila et al., 2012; Nussenzweig and Nussenzweig, 2010; Weinstock et al., 2007; Simsek et al., 2011).”
BackgroundNon-homologous end joining often uses microhomology: Implications for alternative end joining
Pannunzio, N. R., Li, S., Watanabe, G., & Lieber, M. R. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.02.006 · Cited by 115 · cited 2× · see citing works
“The canonical pathway of NHEJ (c-NHEJ) is required for cellular resistance to ionizing radiation aswell as for immune system rearrangements and is active throughout the cell cycle (Deriano and Roth, 2013; Goodarzi and Jeggo, 2013; Pannunzio et al., 2014).”
BackgroundChromosome translocation based on illegitimate recombination in human tumors
Zucman‐Rossi, J., Legoix, P., Victor, J., López, B. S., & Thomas, G. D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11786 · Cited by 110 · cited 5× · see citing works
“…of patient-derived translocations (Gillert et al., 1999; Langer et al., 2003; Reichel et al., 1998; Weinstock et al., 2006; Zhang et al., 2002; Zucman-Rossi et al., 1998), suggesting that cancer translocations may also arise from some other type of DNA end structure. nCas9-induced nicks…”
BackgroundInfluentialGillert, E., Leis, T., Repp, R., Reichel, M., Hösch, A., Breitenlohner, I., Angermüller, S., Borkhardt, A., Harbott, J., Lampert, F. H., et al. (1999) · Oncogene · doi:10.1038/sj.onc.1202842 · Cited by 110 · cited 5× · see citing works
“…of Cas9-induced DSBs means that the translocation junctions often do not exhibit the small deletions typical of patient-derived translocations (Gillert et al., 1999; Langer et al., 2003; Reichel et al., 1998; Weinstock et al., 2006; Zhang et al., 2002; Zucman-Rossi et al., 1998), suggesting…”
BackgroundInfluentialZhang, Y., Strissel, P. L., Strick, R., Chen, J., Nucifora, G., Beau, M. M. L., Larson, R. A., & Rowley, J. D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042702899 · Cited by 109 · see citing works
Soni, A., Siemann, M., Grabos, M., Murmann-Konda, T., Pantelias, G. E., & Iliakis, G. E. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku298 · Cited by 108 · cited 1× · see citing works
“Ionizing radiation, a potent inducer of translocations in rodent cells, does not significantly induce translocations in a LIG4 mutant human cell line (Soni et al., 2014).”
BackgroundXR-1細胞のDNAリガーゼIVタンパクの欠損 XRCC4による安定化の証拠
Bryans, M., Valenzano, M. C., & Stamato, T. D. (1999) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · Cited by 107 · see citing works
A noncatalytic function of the ligation complex during nonhomologous end joining
Jessica, C., Frit, P., Bombarde, O., Salles, B., Négrel, A., Bernard, S., Jeggo, P. A., Lieber, M. R., Modesti, M., & Calsou, P. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201203128 · Cited by 105 · cited 2× · see citing works
“The remaining LIG4 in these cells has residual catalytic activity (O’Driscoll et al., 2001), and it may also promote DNAPKcs bridging activity (Cottarel et al., 2013) to protect ends from extensive degradation.”
BackgroundReichel, M., Gillert, E., Nilson, I., Siegler, G., Greil, J., Fey, G. H., & Marschalek, R. (1998) · Oncogene · doi:10.1038/sj.onc.1202229 · Cited by 100 · cited 4× · see citing works
“…junctions often do not exhibit the small deletions typical of patient-derived translocations (Gillert et al., 1999; Langer et al., 2003; Reichel et al., 1998; Weinstock et al., 2006; Zhang et al., 2002; Zucman-Rossi et al., 1998), suggesting that cancer translocations may also arise…”
BackgroundInfluentialWeinstock, D. M., Elliott, B., & Jasin, M. (2005) · Blood · doi:10.1182/blood-2005-06-2437 · Cited by 91 · cited 4× · see citing works
“Thus, in mouse cells, DSB repair leading to translocations differs from intrachromosomal repair of a single DSB (Simsek and Jasin, 2010; Weinstock et al., 2006), whereas in human cells both types of repair are similar and mediated by c-NHEJ.”
BackgroundInfluentialSelf-citationSCID in Jack Russell Terriers: A New Animal Model of DNA-PKcs Deficiency
Meek, K., Kienker, L. J., Dallas, C., Wang, W., Dark, M. J., Venta, P. J., Huie, M. L., Hirschhorn, R., & Bell, T. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.4.2142 · Cited by 87 · cited 1× · see citing works
“Although NHEJ components are conserved, human cells have substantially higher DNA-PK activity than rodent cells (Finnie et al., 1995; Beamish et al., 2000; Meek et al., 2001).”
BackgroundImpact of DNA ligase IV on the fidelity of end joining in human cells
Smith, J. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg317 · Cited by 78 · cited 3× · see citing works
“Junctions that form by alt-NHEJ have more microhomology and longer deletions than junctions formed by c-NHEJ (Fattah et al., 2010; Guirouilh-Barbat et al., 2007; Kabotyanski et al., 1998; Oh et al., 2013; Simsek and Jasin, 2010; Smith et al., 2003).”
BackgroundLanger, T., Metzler, M., Reinhardt, D., Viehmann, S. F., Borkhardt, A., Reichel, M., Stanulla, M., Schrappe, M., Creutzig, U., Ritter, J., et al. (2003) · Genes Chromosomes and Cancer · doi:10.1002/gcc.10167 · Cited by 78 · cited 2× · see citing works
“…lengths of microhomology lar Cell 55, 829–842, September 18, 2014 ª2014 Elsevier Inc. 829 (legend continued on next page) 830 Molecular Cell 55, 829–842, September 18, 2014 ª2014 Elsevier Inc. (Gillert et al., 1999; Langer et al., 2003; Zucman-Rossi et al., 1998; Mattarucchi et al., 2008).”
BackgroundDifferences in tidal breathing between infants with chronic lung diseases and healthy controls
Schmalisch, G., Wilitzki, S., & Wauer, R. (2005) · BMC Pediatrics · doi:10.1186/1471-2431-5-36 · Cited by 77 · see citing works
Beamish, H. J. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.7.1506 · Cited by 66 · cited 1× · see citing works
“Although NHEJ components are conserved, human cells have substantially higher DNA-PK activity than rodent cells (Finnie et al., 1995; Beamish et al., 2000; Meek et al., 2001).”
BackgroundOh, S., Harvey, A., Zimbric, J., Wang, Y., Nguyen, T., Jackson, P. J., & Hendrickson, E. A. (2014) · DNA Repair · doi:10.1016/j.dnarep.2014.04.015 · Cited by 58 · cited 3× · see citing works
“HCT116 LIG3flox/ cells containing a conditional LIG3 allele and a deletion allele (Oh et al., 2014) were further engineered to express human LIG1 with a mitochondrial leader sequence (MtLIG1).”
BackgroundInfluentialSelf-citationMicrohomologies and interspersed repeat elements at genomic breakpoints in chronic myeloid leukemia
Mattarucchi, E., Guerini, V., Rambaldi, A., Campiotti, L., Venco, A., Pasquali, F., Curto, F. L., & Porta, G. (2008) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20568 · Cited by 54 · cited 1× · see citing works
“…lengths of microhomology lar Cell 55, 829–842, September 18, 2014 ª2014 Elsevier Inc. 829 (legend continued on next page) 830 Molecular Cell 55, 829–842, September 18, 2014 ª2014 Elsevier Inc. (Gillert et al., 1999; Langer et al., 2003; Zucman-Rossi et al., 1998; Mattarucchi et al., 2008).”
BackgroundLow levels of DNA ligases III and IV sufficient for effective NHEJ
Windhofer, F., Wu, W., & Iliakis, G. E. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21120 · Cited by 49 · cited 1× · see citing works
“In patient 411BR cells, the translocation frequency was not affected, consistent with a report that low levels of LIG4 are sufficient for DSB repair in vitro (Windhofer et al., 2007), but deletion lengths were intermediate between control cells and other LIG4 mutants.”
BackgroundOh, S., Wang, Y., Zimbric, J., & Hendrickson, E. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1326 · Cited by 46 · cited 4× · see citing works
“Junctions that form by alt-NHEJ have more microhomology and longer deletions than junctions formed by c-NHEJ (Fattah et al., 2010; Guirouilh-Barbat et al., 2007; Kabotyanski et al., 1998; Oh et al., 2013; Simsek and Jasin, 2010; Smith et al., 2003).”
BackgroundMethodInfluentialSelf-citationSobreira, N. L. M., Gnanakkan, V. P., Walsh, M. F., Marosy, B. A., Wohler, E., THOMAS, G. V., Hoover-Fong, J. E., Hamosh, A., Wheelan, S. J., & Valle, D. L. (2011) · Genome Research · doi:10.1101/gr.122986.111 · Cited by 46 · cited 1× · see citing works
“However, unlike mouse cells, a significant fraction was also derived from other chromosomes, as reported for other human translocations (Piganeau et al., 2013; Sobreira et al., 2011; Zucman-Rossi et al., 1998).”
BackgroundThe Potent Oncogene NPM-ALK Mediates Malignant Transformation of Normal Human CD4+ T Lymphocytes
Zhang, Q., Wei, F., Wang, H. Y., Liu, X., Roy, D. B., Xiong, Q.-B., Jiang, S., Medvec, A. R., Danet-Desnoyers, G. A., Watt, C. D., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.08.030 · Cited by 40 · cited 1× · see citing works
“These results suggest locus effects in the ability to switch from c-NHEJ to alt-NHEJ; alternatively, the oncogenic NPM-ALK fusion protein formed by the translocation could provide a slight growth advantage (Zhang et al., 2013).”
BackgroundBoubakour-Azzouz, I., Bertrand, P., Claës, A., López, B. S., & Rougeon, F. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks585 · Cited by 27 · cited 1× · see citing works
“TdT is required for diversification of antigen receptors, and TdT-generated insertions at these and other DSBs are dependent on c-NHEJ components (Boubakour-Azzouz et al., 2012; Smith et al., 2003).”
Background
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GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3117 · Cited by 2,268 · see citing works
Kosicki, M., Tomberg, K., & Bradley, A. (2018) · Nature Biotechnology · doi:10.1038/nbt.4192 · Cited by 1,883 · see citing works
Non-homologous DNA end joining and alternative pathways to double-strand break repair
Chang, H. H. Y., Pannunzio, N. R., Adachi, N., & Lieber, M. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.48 · Cited by 1,757 · see citing works
Huang, R., & Zhou, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00648-7 · Cited by 948 · see citing works
“In addition, alt-EJ is mainly mediated by the CtIP/ MRN complex.(319) Furthermore, Polθ can indicate the microhomologous DNA ends to support the joining of DNA ends.”
BackgroundPatterns of somatic structural variation in human cancer genomes
Li, Y., Roberts, N. D., Wala, J. A., Shapira, O., Schumacher, S. E., Kumar, K., Khurana, E., Waszak, S., Korbel, J. O., Haber, J. E., et al. (2020) · Nature · doi:10.1038/s41586-019-1913-9 · Cited by 867 · see citing works
“Hypothesis-driven in vitro studies are now beginning to reveal some of the mechanistic processes generating these structures 9–13 , and generate further predictions that can be assessed in the genomics data.”
Mechanisms underlying structural variant formation in genomic disorders
Carvalho, C. M. B., & Lupski, J. R. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2015.25 · Cited by 774 · see citing works
Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?
Sfeir, A., & Symington, L. S. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.08.006 · Cited by 636 · see citing works
Applications of the CRISPR-Cas9 system in cancer biology
Sánchez-Rivera, F. J., & Jacks, T. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3950 · Cited by 405 · see citing works
Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells
Garaycoechea, J. I., Crossan, G. P., Langevin, F., Mulderrig, L., Louzada, S., Yang, F., Guilbaud, G., Park, N., Roerink, S. F., Nik‐Zainal, S., et al. (2018) · Nature · doi:10.1038/nature25154 · Cited by 385 · see citing works
Error‐Prone Repair of DNA Double‐Strand Breaks
Rodgers, K., & McVey, M. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25053 · Cited by 377 · see citing works
“In a recent JOURNAL OF CELLULAR PHYSIOLOGY study using human cells, chromosome translocations were created using a combination of designer nucleases, including ZFNs, TALENs, and CRISPR/Cas9 (Ghezraoui et al., 2014).”
MethodBillon, P., Bryant, E. E., Joseph, S. A., Nambiar, T. S., Hayward, S. B., Rothstein, R., & Ciccia, A. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.008 · Cited by 363 · see citing works
“One common limitation of both NHEJand HDR-dependent gene editing approaches is their reliance on the formation of DSBs, which are toxic DNA lesions that can cause genomic rearrangements and translocations, activate DNA damage checkpoints, and induce cell death (Aguirre et al., 2016; Choi and Meyerson, 2014; Frock et a…”
BackgroundMechanism of Microhomology-Mediated End-Joining Promoted by Human DNA Polymerase Theta
Kent, T., Chandramouly, G., McDevitt, S., Ozdemir, A. Y., & Pomerantz, R. (2015) · Nature Structural &Molecular Biology · doi:10.1038/nsmb.2961 · Cited by 331 · see citing works
CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome
Shin, H. Y., Wang, C., Lee, H., Yoo, K. H., Zeng, X., Kuhns, T. M., Yang, C. M., Mohr, T., Liu, C., & Hennighausen, L. G. (2017) · Nature Communications · doi:10.1038/ncomms15464 · Cited by 303 · see citing works
Ly, P., Teitz, L. S., Kim, D. H., Shoshani, O., Skaletsky, H., Fachinetti, D., Page, D. C., & Cleveland, D. W. (2016) · Nature Cell Biology · doi:10.1038/ncb3450 · Cited by 279 · 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
“NHEJ is error prone because end processing can lead to small base pair deletions and translocations (Ghezraoui et al., 2014; Lieber, 2010).”
BackgroundMladenov, E., Magin, S., Soni, A., & Iliakis, G. E. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2016.03.003 · Cited by 252 · see citing works
Microhomology-mediated end joining: Good, bad and ugly
Seol, J.-H., Shim, E. Y., & Lee, S. E. (2017) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2017.07.002 · Cited by 249 · see citing works
“However, in human cells, the formation of chromosomal translocations is not dependent on MMEJ factors but is dependent on C-NHEJ factors, including Ligase IV [74].”
BackgroundMethodInfluentialMultiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM
Wong, A. S. L., Choi, G. C. G., Cui, C. H., Pregernig, G., Milani, P., Adam, M., Perli, S. D., Kazer, S. W., Gaillard, A., Hermann, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1517883113 · Cited by 236 · see citing works
“Such discrepancies could be partially due to variations in chromatin accessibility at target loci (22) and DNA break repair mechanisms (23) that can vary among cell types.”
BackgroundRepair of DNA double-strand breaks by mammalian alternative end-joining pathways
Sallmyr, A., & Tomkinson, A. E. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000375 · Cited by 228 · see citing works
“arise as a consequence of the repair of DSBs by NHEJ (88).”
BackgroundSelf-citationJasin, M., & Haber, J. E. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.05.001 · Cited by 220 · see citing works
“NHEJ pathway appears to be involved when nicks are offset to generate 5’ overhangs [60, 181].”
BackgroundSelf-citationRepair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway
Stinson, B. M., & Loparo, J. J. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-080320-110356 · Cited by 223 · see citing works
Diemer-Biehs, R., Steinlage, M., Barton, O., Juhász, S., Künzel, J., Spies, J., Shibata, A., Jeggo, P. A., & Löbrich, M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2016.12.016 · Cited by 201 · see citing works
“See also Figure S3. employing designer nucleases (Ghezraoui et al., 2014).”
BackgroundRebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis
Ly, P., & Cleveland, D. W. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.08.005 · Cited by 205 · see citing works
“Chromosomal translocations in human cells are mediated primarily through c-NHEJ, although murine cells appear to favor alternative-EJ (alt-EJ) [53,54].”
Tu, T., Budzinska, M. A., Vondran, F. W. R., Shackel, N. A., & Urban, S. (2018) · Journal of Virology · doi:10.1128/jvi.02007-17 · Cited by 205 · see citing works
Iliakis, G. E., Murmann-Konda, T., & Soni, A. (2015) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2015.07.001 · Cited by 199 · see citing works
CRISPR-Cas9: a new and promising player in gene therapy
Xiao-Jie, L., Hui-Ying, X., Zun-Ping, K., Jin-Lian, C., & Li-Juan, J. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102968 · Cited by 200 · see citing works
Clustered DNA Double-Strand Breaks: Biological Effects and Relevance to Cancer Radiotherapy
Nickoloff, J. A., Sharma, N., & Taylor, L. E. (2020) · Genes · doi:10.3390/genes11010099 · Cited by 198 · see citing works
“There is substantial evidence that chromosome translocations are frequently mediated by aNHEJ [27], although other evidence suggests that cNHEJ can mediate translocations in human cells [117].”
BackgroundCRISPaint allows modular base-specific gene tagging using a ligase-4-dependent mechanism
Schmid-Burgk, J. L., Höning, K., Ebert, T. S., & Hornung, V. (2016) · Nature Communications · doi:10.1038/ncomms12338 · Cited by 190 · see citing works
Shou, J., Li, J., Liu, Y., & Wu, Q. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.021 · Cited by 187 · see citing works
Marker-free coselection for CRISPR-driven genome editing in human cells
Agudelo, D., Duringer, A., Bozoyan, L., Huard, C., Carter, S., Loehr, J., Synodinou, D., Drouin, M., Salsman, J., Dellaire, G., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4265 · Cited by 174 · see citing works
The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer
Sishc, B. J., & Davis, A. J. (2017) · Cancers · doi:10.3390/cancers9070081 · Cited by 178 · see citing works
CRISPR–Cas: a tool for cancer research and therapeutics
Yin, H., Xue, W., & Anderson, D. G. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0166-8 · Cited by 178 · see citing works
Bacolla, A., Tainer, J. A., Vásquez, K. M., & Cooper, D. N. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw261 · Cited by 164 · see citing works
“Two pathways, microhomology-mediated end joining (MMEJ), also referred to as alternative NHEJ (altNHEJ), and single-strand annealing (SSA) share with HR the initial steps of end processing and end resection, but diverge at subsequent steps and use either minimal (generally fewer than a dozen bases for MMEJ) or substan…”
BackgroundSliding sleeves of XRCC4–XLF bridge DNA and connect fragments of broken DNA
Brouwer, I., Sitters, G., Candelli, A., Heerema, S. J., Heller, I., de Melo, A. J., Zhang, H., Normanno, D., Modesti, M., Peterman, E. J. G., et al. (2016) · Nature · doi:10.1038/nature18643 · Cited by 166 · see citing works
Advances in CRISPR-Cas9 genome engineering: lessons learned from RNA interference
Barrangou, R., Birmingham, A., Wiemann, S., Beijersbergen, R. L., Hornung, V., & Smith, A. V. B. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv226 · Cited by 164 · see citing works
Imprecision and DNA Break Repair Biased towards Incompatible End Joining in Leukemia
Gassner, F. J., Schubert, M., Rebhandl, S., Spandl, K., Zaborsky, N., Catakovic, K., Blaimer, S., Hebenstreit, D., Greil, R., & Geisberger, R. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0373 · Cited by 156 · see citing works
“To a lesser extent also, inhibition of LIG1/3 showed an effect on direct pGFP-1/pGFP-2 joining, while inhibition of PARP family proteins by olaparib had no effect on DNA repair in this assay (Fig.”
BackgroundInfluentialStudying DNA Double-Strand Break Repair: An Ever-Growing Toolbox
Vítor, A. C., Huertas, P., Legube, G., & de Almeida, S. F. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00024 · Cited by 148 · see citing works
“Using this system, the Kastan lab disclosed the distribution of Nbs1 and ATM, and histones (Berkovich et al., 2007; Goldstein et al., 2013) at DSBs by ChIP-qPCR.”
MethodTadi, S. K., Sebastian, R., Dahal, S., Babu, R. K., Choudhary, B., & Raghavan, S. C. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-05-0260 · Cited by 146 · see citing works
“Such observations have not yet been confirmed in human cells (Roth, 2002; Zhu et al., 2002; Ghezraoui et al., 2014).”
BackgroundGuo, T., Feng, Y.-L., Xiao, J., Liu, Q., Sun, X., Xiang, J.-F., Kong, N., Liu, S., Chen, G., Wang, Y., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1518-x · Cited by 143 · see citing works
DNA Damage in Cancer Therapeutics: A Boon or a Curse?
Khanna, A. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3247 · Cited by 140 · see citing works
“(iii) The damaged DNA is misrepaired and the cell evades senescence and death, resulting in apopulation of cells that carries deleteriousmutations or chromosomal aberrations with oncogenic potential (5, 6).”
BackgroundNoncanonical views of homology-directed DNA repairPreprint
Verma, P., & Greenberg, R. A. (2016) · Genes & Development · doi:10.1101/gad.280545.116 · Cited by 139 · see citing works
“While MMEJ is the predominant pathway in mice for chromosomal translocations, recent studies demonstrated that translocations in humans are primarily mediated by c-NHEJ (Simsek and Jasin 2010; Ghezraoui et al. 2014).”
BackgroundMechanisms of human lymphoid chromosomal translocations
Lieber, M. R. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.40 · Cited by 137 · see citing works
“Multiple myeloma (14%) • CCND1–IGH t(11;14)(q13;q32) • WHSC1–IGH t(4;14)(q32;q21) • TAF8–IGH t(6;14)(p21;q32) • MAFB–IGH t(14;20)(q32;q12) • WWOX–IGH t(14;16)(q32;q23) Hodgkin lymphoma (7%) Other lymphoma (10%) Diffuse large B cell lymphoma (18%) • BCL6–IGH t(3;14)(q27;q32) 20% • BCL2–IGH t(14;18)(q32;q21) 20% • BCL6–…”
Cebrian-Serrano, A., & Davies, B. (2017) · Mammalian Genome · doi:10.1007/s00335-017-9697-4 · Cited by 135 · see citing works
UDiTaS™, a genome editing detection method for indels and genome rearrangements
Giannoukos, G., Ciulla, D., Marco, E., Abdulkerim, H. S., Barrera, L. A., Bothmer, A., Dhanapal, V., Gloskowski, S. W., Jayaram, H., Maeder, M. L., et al. (2018) · BMC Genomics · doi:10.1186/s12864-018-4561-9 · Cited by 131 · see citing works
Templated Insertions: A Smoking Gun for Polymerase Theta-Mediated End Joining.
Schimmel, J., van Schendel, R., den Dunnen, J. D., & Tijsterman, M. (2019) · Trends in Genetics · doi:10.1016/j.tig.2019.06.001 · Cited by 130 · see citing works
Modulating DNA Repair Pathways to Improve Precision Genome Engineering
Pawelczak, K. S., Gavande, N. S., VanderVere-Carozza, P. S., & Turchi, J. J. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.7b00777 · Cited by 132 · see citing works
CRISPR/Cas9‐mediated genome editing: From basic research to translational medicine
Jacinto, F. V., Link, W., & Ferreira, B. I. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14916 · Cited by 130 · see citing works
A role for human homologous recombination factors in suppressing microhomology-mediated end joining
Ahrabi, S., Sarkar, S., Pfister, S. X., Pirovano, G., Higgins, G. S., Porter, A. C. G., & Humphrey, T. C. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw326 · Cited by 122 · see citing works
“MMEJ is mediated via CtIP, MRN complex, Poly [ADP-ribose] polymerases1 (PARP-1) and DNA ligase 3 (Lig 3) (29,30).”
MethodMapping of Wnt‐Frizzled interactions by multiplex CRISPR targeting of receptor gene families
Voloshanenko, O., Gmach, P., Winter, J., Kranz, D., & Boutros, M. (2017) · The FASEB Journal · doi:10.1096/fj.201700144r · Cited by 118 · see citing works
Precision cancer mouse models through genome editing with CRISPR-Cas9
Mou, H., Kennedy, Z., Anderson, D. G., Yin, H., & Xue, W. (2015) · Genome Medicine · doi:10.1186/s13073-015-0178-7 · Cited by 113 · see citing works
“These rearrangements have been generated by CRISPR-Cas9 technology [20, 38].”
MethodA Process of Resection-Dependent Nonhomologous End Joining Involving the Goddess Artemis
Löbrich, M., & Jeggo, P. A. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.06.011 · Cited by 114 · see citing works
Creating and evaluating accurate CRISPR-Cas9 scalpels for genomic surgery
Bolukbasi, M. F., Gupta, A., & Wolfe, S. A. (2015) · Nature Methods · doi:10.1038/nmeth.3684 · Cited by 111 · see citing works
A glance at genome editing with CRISPR–Cas9 technology
Barman, A., Deb, B., & Chakraborty, S. (2019) · Current Genetics · doi:10.1007/s00294-019-01040-3 · Cited by 105 · see citing works
A Multidrug-resistant Engineered CAR T Cell for Allogeneic Combination Immunotherapy
Valton, J., Guyot, V., Maréchal, A., Filhol, J.-M., Juillerat, A., Duclert, A., Duchateau, P. N., & Poirot, L. (2015) · Molecular Therapy · doi:10.1038/mt.2015.104 · Cited by 109 · see citing works
DNA double strand break repair pathway choice: a chromatin based decision?
Clouaire, T., & Legube, G. (2015) · Nucleus · doi:10.1080/19491034.2015.1010946 · Cited by 108 · see citing works
Life or Death after a Break: What Determines the Choice?
Krenning, L., van den Berg, J., & Medema, R. H. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.08.023 · Cited by 108 · see citing works
Comparison of the Feasibility, Efficiency, and Safety of Genome Editing Technologies
Castro, N. G. G., Bjelic, J., Malhotra, G., Huang, C., & Alsaffar, S. H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910355 · Cited by 107 · see citing works
“Moreover, methylation of c tosine ca alter recogniti n by its norm l RVD and potentially brogate TALE binding altog ther ( different RVD capable of recognising 5′mC w uld be required) [41, 4,45].”
BackgroundIliakis, G. E., Mladenov, E., & Mladenova, V. (2019) · Cancers · doi:10.3390/cancers11111671 · Cited by 101 · see citing works
“As a result, c-NHEJ can catalyze the formation of translocations [15,16].”
BackgroundCross talk of tyrosine kinases with the DNA damage signaling pathways
Mahajan, K. N., & Mahajan, N. P. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1166 · Cited by 101 · see citing works
How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability
Jeggo, P. A., & Löbrich, M. (2015) · Biochemical Journal · doi:10.1042/bj20150582 · Cited by 100 · see citing works
CRISPR engineering in organoids for gene repair and disease modelling
Geurts, M. H., & Clevers, H. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-022-00013-5 · Cited by 103 · see citing works
C-NHEJ without indels is robust and requires synergistic function of distinct XLF domains
Bhargava, R., Sandhu, M., Muk, S., Lee, G., Vaidehi, N., & Stark, J. M. (2018) · Nature Communications · doi:10.1038/s41467-018-04867-5 · Cited by 93 · see citing works
Structural Variation in Cancer: Role, Prevalence, and Mechanisms
Cosenza, M. R., Rodríguez–Martín, B., & Korbel, J. O. (2022) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120121-101149 · Cited by 92 · see citing works
Ligase I and ligase III mediate the DNA double-strand break ligation in alternative end-joining
Lu, G., Duan, J., Shu, S., Wang, X., Gao, L., Guo, J., & Zhang, Y. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521597113 · Cited by 94 · see citing works
“For example, it has been suggested that A-EJ is the main end-joining activity to catalyze chromosomal translocations in murine (15) but not in human cells (16).”
BackgroundDNA Polymerase θ: A Unique Multifunctional End-Joining Machine
Black, S., Kashkina, E., Kent, T., & Pomerantz, R. T. (2016) · Genes · doi:10.3390/genes7090067 · Cited by 93 · see citing works
“, ≥2 bp in human cells) of sequence microhomology which may promote base pairing of complementary portions of 3’ ssDNA overhangs (Figure 2, right; Table 1) [51].”
BackgroundResultInfluentialIn vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model
Carreras, A., Pane, L. S., Nitsch, R., Madeyski-Bengtson, K., Porritt, M. J., Akçakaya, P., Taheri‐Ghahfarokhi, A., Ericson, E., Bjursell, M., Pérez-Alcázar, M., et al. (2019) · BMC Biology · doi:10.1186/s12915-018-0624-2 · Cited by 92 · see citing works
“Chromosomal translocations, which result from double-strand breaks in chromosomes and subsequent joining of loose ends of different chromosome arms, may limit the therapeutic use of genomic editing technologies because of their oncogenic potential [43, 44].”
BackgroundA Model Linking Sickle Cell Hemoglobinopathies and SMARCB1 Loss in Renal Medullary Carcinoma
Msaouel, P., Tannir, N. M., & Walker, C. L. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3296 · Cited by 87 · see citing works
“However, while cNHEJ suppresses translocations in mice, it has recently been found to produce oncogenic chromosomal translocations in humans (21, 28).”
BackgroundIn vivo blunt-end cloning through CRISPR/Cas9-facilitated non-homologous end-joining
Geisinger, J. M., Turan, S., Hernandez, S., Spector, L. P., & Calos, M. P. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1542 · Cited by 83 · see citing works
“(5,6,20,26,36,77) underscore that NHEJ resulting from blunt-end, chemically unmodified DSBs, such as those made by Cas9, are repaired with a high degree of precision.”
InfluentialWhen 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
Self-citationA novel small molecule inhibitor of the DNA repair protein Ku70/80
Weterings, E., Gallegos, A. C., Dominick, L. N., Cooke, L. S., Bartels, T. N., Vágner, J., Matsunaga, T. O., & Mahadevan, D. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.03.014 · Cited by 84 · see citing works
Brunet, E., & Jasin, M. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0593-1_2 · Cited by 78 · see citing works
“Modeling t(2;5)(p23;q35), found in cases of ALCL, our group showed expression of oncogenic NPM1-ALK kinase activation in human cell lines.”
BackgroundMethodInfluentialSelf-citationVriend, L. E. M., Prakash, R., Chen, C.-C., Vanoli, F., Cavallo, F., Zhang, Y., Jasin, M., & Krawczyk, P. M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw179 · Cited by 78 · see citing works
“In agreement, single Cas9-generated nicks fail to induce oncogenic chromosomal translocations, which require DSB formation (68).”
BackgroundSelf-citationGenetic and Epigenetic Alterations in Bladder Cancer
Li, H., Duymich, C. E., Weisenberger, D. J., & Liang, G. (2016) · International Neurourology Journal · doi:10.5213/inj.1632752.376 · Cited by 79 · see citing works
“Chromosomal Rearrangements Chromosomal rearrangements, namely the concomitant result of aberrant nonhomologous end joining [33], may result in oncogene formation and therefore may initiate tumorigenesis [30,34] or increasing oncogene expression [35].”
BackgroundKitano, Y., Nishimura, S., Kato, T., Ueda, A., Takigawa, K., Umekage, M., Nomura, M., Kawakami, A., Ogawa, H., Xu, H., et al. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.05.010 · Cited by 80 · see citing works
“There is also a risk of chromosomal translocation when double-strand breaks are introduced into different chromosomes.(20,21) Multiplexed gene disruption is necessary for the generation of hypoimmunogenic iPSCs.”
Nilsson, D., Pettersson, M., Gustavsson, P., Förster, A., Hofmeister, W., Wincent, J., Zachariadis, V., Anderlid, B., Nordgren, A., Mäkitie, O., et al. (2016) · Human Mutation · doi:10.1002/humu.23146 · Cited by 74 · see citing works
“…notion that mechanisms other than NHEJ and NAHR underlie the formation of some balanced translocations is provided by studies on human cells, 6% of translocation junctions generated in vitro show the presence of templated insertions varying from 20 bp to several hundred bp [Ghezraoui et al., 2014].”
BackgroundInfluentialRegulation of Error-Prone DNA Double-Strand Break Repair and Its Impact on Genome Evolution
Hanscom, T., & McVey, M. (2020) · Cells · doi:10.3390/cells9071657 · Cited by 70 · see citing works
“For example, in human cells, cNHEJ is responsible for a majority of chromosomal translocations resulting from ionizing radiation and nuclease-induced breaks [14].”
BackgroundRepair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ
Yu, W., Lescale, C., Babin, L., Bedora-Faure, M., Hasse, H. L., Baron, L., Demangel, C., Yélamos, J., Brunet, E., & Deriano, L. (2020) · Nature Communications · doi:10.1038/s41467-020-19060-w · Cited by 68 · see citing works
Self-citationStrategies for Efficient Genome Editing Using CRISPR-Cas9
Farboud, B., Severson, A. F., & Meyer, B. J. (2018) · Genetics · doi:10.1534/genetics.118.301775 · Cited by 64 · see citing works
Targeted genomic translocations and inversions generated using a paired prime editing strategy
Kweon, J., Hwang, H., Ryu, H., Jang, A.-H., Kim, D., & Kim, Y. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.09.008 · Cited by 67 · see citing works
CRISPR-induced double-strand breaks trigger recombination between homologous chromosome arms
Brunner, E., Yagi, R., Debrunner, M., Beck-Schneider, D., Burger, A., Escher, E., Mosimann, C., Hausmann, G., & Basler, K. (2019) · Life Science Alliance · doi:10.26508/lsa.201800267 · Cited by 65 · see citing works
“Because Cas9 activity may often cause the break of both homologs, such recombination events may not only be based on homologous recombination but may also result by breakage/fusion events involving NHEJ that lead to a crosswise ligation of the chromosome arms (15, 16, 17, 18, 19, 20, 21, 22).”
BackgroundThe genomic landscape of 8-oxodG reveals enrichment at specific inherently fragile promoters
Gorini, F., Scala, G., Di Palo, G., Dellino, G. I., Cocozza, S., Pelicci, P. G., Lania, L., Majello, B., & Amente, S. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa175 · Cited by 67 · see citing works
“Since NHEJ is considered an error-prone repair pathway (66), and MCF10A promoter introns (i.”
BackgroundRisky business: Microhomology-mediated end joining
Sinha, S., Villarreal, D. D., Shim, E. Y., & Lee, S. E. (2016) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2015.12.005 · Cited by 66 · see citing works
Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome
Lecoq, A.-L., Stratakis, C. A., Viengchareun, S., Chaligné, R., Tosca, L., Deméocq, V., Hage, M. P., Berthon, A. S., Faucz, F. R., Hanna, P., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.92184 · Cited by 65 · see citing works
“In both adenoma samples, breakpoints close to the GIPR gene were characterized at base pair resolution by conventional Sanger sequencing of the PCR fragments (Figure 3B), showing a junction of canonical nonhomologous end-joining typical of chromosomal translocations in human cells (14).”
BackgroundThe Determinant of DNA Repair Pathway Choices in Ionising Radiation‐Induced DNA Double‐Strand Breaks
Zhao, L., Bao, C., Shang, Y., He, X., Ma, C., Lei, X., Mi, D., & Sun, Y. (2020) · BioMed Research International · doi:10.1155/2020/4834965 · Cited by 65 · see citing works
A versatile reporter system for CRISPR-mediated chromosomal rearrangements
Li, Y., Park, A. I., Mou, H., Colpan, C., Bizhanova, A., Akama‐Garren, E. H., Joshi, N., Hendrickson, E. A., Feldser, D. M., Yin, H., et al. (2015) · Genome biology · doi:10.1186/s13059-015-0680-7 · Cited by 64 · see citing works
“The role of LIG4 in mediating the rearrangements and the application of CRISPR-Cas9 to induce inversions and deletions in cells and in mice have been reported by recent studies [16, 19, 21, 31].”
BackgroundMethodInfluentialSelf-citationGenomic 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
Guo, C., Nakazawa, Y., Woodbine, L. J., Björkman, A., Shimada, M., Fawcett, H., Jia, N., Ohyama, K., Li, T., Nagayama, Y., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.06.007 · Cited by 63 · see citing works
On- and off-target effects of paired CRISPR-Cas nickase in primary human cells
Klermund, J., Rhiel, M., Köcher, T., Chmielewski, K. O., Bischof, J., Andrieux, G., el Gaz, M., Hainzl, S., Boerries, M., Cornu, T. I., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.006 · Cited by 62 · see citing works
“26,37,42 Furthermore, in cells edited with paired CRISPR-Cas9 nickases, translocations between the target site and known off-target sites could not be detected by qualitative translocation PCR. 38 However, a systematic genome-wide and sensitive analysis of on-and off-target aberrations in…”
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
Mechanisms of germ line genome instability
Kim, S., Peterson, S., Jasin, M., & Keeney, S. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.02.019 · Cited by 58 · see citing works
Self-citationVanoli, F., Tomishima, M. J., Feng, W., Lamribet, K., Babin, L., Brunet, E., & Jasin, M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700622114 · Cited by 56 · see citing works
“Spraggon L, et al. (2017) Generation of conditional oncogenic chromosomal translocations using CRISPR-Cas9 genomic editing and homology-directed repair.”
BackgroundInfluentialSelf-citationSchipler, A., Mladenova, V., Soni, A., Nikolov, V., Saha, J., Mladenov, E., & Iliakis, G. E. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw487 · Cited by 56 · see citing works
“Since HRR is unlikely to catalyze their formation, c-NHEJ and alt-EJ become natural candidates, with alt-EJ featuring more prominently, although the actual relative contribution is debated and likely to also be cell-cycle-phase and DSB-site dependent (16,44,51).”
Han, J., Ruan, C., Huen, M. S. Y., Wang, J., Xie, A., Fu, C. M., Liu, T., & Huang, J. (2017) · Nature Communications · doi:10.1038/s41467-017-01759-y · Cited by 55 · see citing works
Detection and Modulation of DNA Translocations During Multi-Gene Genome Editing in T Cells
Bothmer, A., Gareau, K. W., Abdulkerim, H. S., Buquicchio, F. A., Cohen, L. A., Viswanathan, R., Zuris, J. A., Marco, E., Fernández, C. A., Myer, V. E., et al. (2020) · The CRISPR Journal · doi:10.1089/crispr.2019.0074 · Cited by 53 · see citing works
“29 We reasoned that if we engaged ‰ Fig.”
From gene editing to genome engineering: restructuring plant chromosomes via CRISPR/Cas
Schmidt, C., Schindele, P., & Puchta, H. (2019) · aBIOTECH · doi:10.1007/s42994-019-00002-0 · Cited by 52 · 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
CRISPR therapeutic tools for complex genetic disorders and cancer (Review)
Baliou, S., Adamaki, M., Kyriakopoulos, A. M., Spandidos, D. A., Panayiotidis, M. I., Christodoulou, I., & Zoumpourlis, V. C. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4434 · Cited by 48 · see citing works
“In addition, the chromosomal translocation t(8;21)/RUNX1-ETO was introduced into 293 cells and CD34+ human hematopoietic progenitor cells with the use of the CRISPR system, successfully recapitulating the phenotype of acute myeloid leukemia (AML).”
InfluentialDiscovery and development of novel DNA-PK inhibitors by targeting the unique Ku–DNA interaction
Gavande, N. S., VanderVere-Carozza, P. S., Pawelczak, K. S., Mendoza-Munoz, P. L., Vernon, T. L., Hanakahi, L. A., Summerlin, M., Dynlacht, J. R., Farmer, A. H., Sears, C. R., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa934 · Cited by 46 · see citing works
“It is well understood that random insertion of a dsDNA molecule, a technique utilized for generating stably transfected cell lines for decades, is driven by NHEJ (48;52-55).”
BackgroundSpecificity of oligonucleotide gene therapy (OGT) agents
Nedorezova, D. D., Dubovichenko, M. V., Belyaeva, E. P., Grigorieva, E. D., Peresadina, A. V., & Kolpashchikov, D. M. (2022) · Theranostics · doi:10.7150/thno.77830 · Cited by 48 · see citing works
Biechonski, S., Yassin, M., & Milyavsky, M. (2017) · Carcinogenesis · doi:10.1093/carcin/bgx002 · Cited by 47 · see citing works
“This pathway is considered fast but error prone, which may account for most of the genomic structural variants and chromosomal translocations found in human cancer (68,69).”
Background
- Authors
- Ghezraoui, H., Piganeau, M., Renouf, B., Renaud, J.-B., Sallmyr, A., Ruis, B., Oh, S., Tomkinson, A. E., Hendrickson, E. A., Giovannangeli, C., Jasin, M., & Brunet, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of New Mexico (US)
- University of Minnesota (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Jasin, Maria
- Brunet, Erika
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 55
- Issue
- 6
- Pages
- 829-842
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4398060
- OpenAlex
- W2080290623
- Cited by
- 351
- References
- 68
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 27 · 2023: 24 · 2022: 29 · 2021: 26 · 2020: 33 · 2019: 31 · 2018: 33 · 2017: 38 · 2016: 43 · 2015: 40 · 2014: 2
- FWCI
- 16.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-12, ANR-12-JSV6-0005)
- Ligue Contre le Cancer
- Muséum National d'Histoire Naturelle
- National Institutes of Health (GM047251)
- National Cancer Institute (CA15446, P30CA118100, P01CA092584)
- National Institute of General Medical Sciences (R01GM047251, GM047251, R01GM088351, GM088351, R01GM054668, GM054668)
- National Institute of Environmental Health Sciences (ES012512, R01ES012512)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- chromosomal translocation, non-homologous end joining, alternative NHEJ, DNA ligase IV, XRCC4, breakpoint junctions, microhomology, DNA double-strand breaks, designer nucleases, CRISPR/Cas9, species differences, human cells
- MeSH terms
- DNA Ligase ATP, Animals, Chromosomes, Human, Deoxyribonucleases, DNA-Binding Proteins, Humans, DNA Ligases, Species Specificity, Translocation, Genetic, Tumor Cells, Cultured, Sequence Deletion, Mice, DNA End-Joining Repair
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