Stephens, P. J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27–40 (2011).
Cortes-Ciriano, I. et al. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat. Genet. 52, 331–341 (2020).
Zhang, C. Z. et al. Chromothripsis from DNA damage in micronuclei. Nature 522, 179–184 (2015).
Ly, P. et al. Chromosome segregation errors generate a diverse spectrum of simple and complex genomic rearrangements. Nat. Genet. 51, 705–715 (2019).
Maciejowski, J. et al. APOBEC3-dependent kataegis and TREX1-driven chromothripsis during telomere crisis. Nat. Genet. 52, 884–890 (2020).
Maciejowski, J., Li, Y., Bosco, N., Campbell, P. J. & de Lange, T. Chromothripsis and kataegis induced by telomere crisis. Cell 163, 1641–1654 (2015).
Umbreit, N. T. et al. Mechanisms generating cancer genome complexity from a single cell division error. Science 368, eaba0712 (2020).
Ly, P. et al. Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining. Nat. Cell Biol. 19, 68–75 (2017).
Crasta, K. et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature 482, 53–58 (2012).
Kato, H. & Sandberg, A. A. Chromosome pulverization in human cells with micronuclei. J. Natl Cancer Inst. 40, 165–179 (1968).
Bakhoum, S. F. & Cantley, L. C. The multifaceted role of chromosomal instability in cancer and its microenvironment. Cell 174, 1347–1360 (2018).
Shoshani, O. et al. Chromothripsis drives the evolution of gene amplification in cancer. Nature Genet. 52, 331–341 (2020).
Kloosterman, W. P. et al. Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer. Genome Biol. 12, R103 (2011).
Molenaar, J. J. et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 483, 589–593 (2012).
Teles Alves, I. et al. Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line. Hum. Genet. 132, 709–713 (2013).
Ly, P. & Cleveland, D. W. Rebuilding chromosomes after catastrophe: emerging mechanisms of chromothripsis. Trends Cell. Biol. 27, 917–930 (2017).
Tang, S., Stokasimov, E., Cui, Y. & Pellman, D. Breakage of cytoplasmic chromosomes by pathological DNA base excision repair. Nature 606, 930–936 (2022).
Stucki, M. et al. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123, 1213–1226 (2005).
Clouaire, T. et al. Comprehensive mapping of histone modifications at DNA double-strand breaks deciphers repair pathway chromatin signatures. Mol. Cell 72, 250–262 (2018).
Iacovoni, J. S. et al. High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome. EMBO J. 29, 1446–1457 (2010).
Soto, M. et al. p53 Prohibits propagation of chromosome segregation errors that produce structural aneuploidies. Cell Rep. 19, 2423–2431 (2017).
Santaguida, S. et al. Chromosome mis-segregation generates cell-cycle-arrested cells with complex karyotypes that are eliminated by the immune system. Dev. Cell 41, 638–651 (2017).
Hatch, E. M. & Hetzer, M. W. Linking micronuclei to chromosome fragmentation. Cell 161, 1502–1504 (2015).
Minocherhomji, S. et al. Replication stress activates DNA repair synthesis in mitosis. Nature 528, 286–290 (2015).
Lobachev, K., Vitriol, E., Stemple, J., Resnick, M. A. & Bloom, K. Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr. Biol. 14, 2107–2112 (2004).
Kaye, J. A. et al. DNA breaks promote genomic instability by impeding proper chromosome segregation. Curr. Biol. 14, 2096–2106 (2004).
Clay, D. E., Bretscher, H. S., Jezuit, E. A., Bush, K. B. & Fox, D. T. Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation. J. Cell Biol. 220, e202106116 (2021).
de Jager, M. et al. Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol. Cell 8, 1129–1135 (2001).
De Marco Zompit, M. et al. The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis. Nat. Commun. 13, 4143 (2022).
Leimbacher, P. A. et al. MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis. Mol. Cell 74, 571–583 (2019).
Adam, S. et al. The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer. Nat. Cancer 2, 1357–1371 (2021).
Laine, A. et al. CIP2A interacts with TopBP1 and drives basal-like breast cancer tumorigenesis. Cancer Res. 81, 4319–4331 (2021).
Wardlaw, C. P., Carr, A. M. & Oliver, A. W. TopBP1: a BRCT-scaffold protein functioning in multiple cellular pathways. DNA Repair (Amst.) 22, 165–174 (2014).
Nabet, B. et al. The dTAG system for immediate and target-specific protein degradation. Nat. Chem. Biol. 14, 431–441 (2018).
Kim, J. E., McAvoy, S. A., Smith, D. I. & Chen, J. Human TopBP1 ensures genome integrity during normal S phase. Mol. Cell. Biol. 25, 10907–10915 (2005).
Bagge, J., Oestergaard, V. H. & Lisby, M. Functions of TopBP1 in preserving genome integrity during mitosis. Semin. Cell Dev. Biol. 113, 57–64 (2021).
Gallina, I., Christiansen, S. K., Pedersen, R. T., Lisby, M. & Oestergaard, V. H. TopBP1-mediated DNA processing during mitosis. Cell Cycle 15, 176–183 (2016).
Pedersen, R. T., Kruse, T., Nilsson, J., Oestergaard, V. H. & Lisby, M. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells. J. Cell Biol. 210, 565–582 (2015).
Junttila, M. R. et al. CIP2A inhibits PP2A in human malignancies. Cell 130, 51–62 (2007).
Hoadley, K. A. et al. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 173, 291–304 (2018).
Yang, J. et al. CTLPScanner: a web server for chromothripsis-like pattern detection. Nucleic Acids Res. 44, W252–W258 (2016).
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes. Nature 578, 82–93 (2020).
Steele, C. D. et al. Signatures of copy number alterations in human cancer. Nature 606, 984–991 (2022).
Groelly, F. J., Fawkes, M., Dagg, R. A., Blackford, A. N. & Tarsounas, M. Targeting DNA damage response pathways in cancer. Nat. Rev. Cancer 23, 78–94 (2023).
Papathanasiou, S. et al. Transgenerational transcriptional heterogeneity from cytoplasmic chromatin. Preprint at bioRxivhttps://doi.org/10.1101/2022.01.12.475869 (2022).
Frattini, C. et al. TopBP1 assembles nuclear condensates to switch on ATR signaling. Mol. Cell 81, 1231–1245 (2021).
Kim, A. et al. Biochemical analysis of TOPBP1 oligomerization. DNA Repair (Amst.) 96, 102973 (2020).
Korbel, J. O. & Campbell, P. J. Criteria for inference of chromothripsis in cancer genomes. Cell 152, 1226–1236 (2013).
Khanna, A. & Pimanda, J. E. Clinical significance of cancerous inhibitor of protein phosphatase 2A in human cancers. Int. J. Cancer 138, 525–532 (2016).
Knijnenburg, T. A. et al. Genomic and molecular landscape of DNA damage repair deficiency across The Cancer Genome Atlas. Cell Rep. 23, 239–254 (2018).
More News
Author Correction: A high-density and high-confinement tokamak plasma regime for fusion energy – Nature
Superstar porous materials get salty thanks to computer simulations
Metals strengthen with increasing temperature at extreme strain rates – Nature