chromosome breakage

Summary

Summary: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.

Top Publications

  1. Holland A, Cleveland D. Chromoanagenesis and cancer: mechanisms and consequences of localized, complex chromosomal rearrangements. Nat Med. 2012;18:1630-8 pubmed publisher
    ..Complex rearrangements are present in a broad spectrum of tumors and in individuals with congenital or developmental defects, highlighting the impact of chromoanagenesis on human disease...
  2. Tsai A, Lu H, Raghavan S, MUSCHEN M, Hsieh C, Lieber M. Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity. Cell. 2008;135:1130-42 pubmed publisher
  3. Kerrest A, Anand R, Sundararajan R, Bermejo R, Liberi G, Dujon B, et al. SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination. Nat Struct Mol Biol. 2009;16:159-67 pubmed publisher
    ..In the absence of Srs2 or Sgs1, DNA damage accumulates and is processed by homologous recombination, triggering repeat rearrangements...
  4. Arlt M, Glover T. Inhibition of topoisomerase I prevents chromosome breakage at common fragile sites. DNA Repair (Amst). 2010;9:678-89 pubmed publisher
    ..These data from cultured human cells demonstrate that topoisomerase I activity is required for DNA common fragile site breaks and suggest that polymerase-helicase uncoupling is a key initial event in this process...
  5. Riera Lizarazu O, Leonard J, Tiwari V, Kianian S. A method to produce radiation hybrids for the D-genome chromosomes of wheat (Triticum aestivum L.). Cytogenet Genome Res. 2010;129:234-40 pubmed publisher
    Radiation hybrid (RH) mapping is based on radiation-induced chromosome breakage rather than meiotic recombination, as a means to induce marker segregation for mapping...
  6. Ou Z, Stankiewicz P, Xia Z, Breman A, Dawson B, Wiszniewska J, et al. Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes. Genome Res. 2011;21:33-46 pubmed publisher
    ..Furthermore, we provide a computationally determined genome-wide "recurrent translocation map."..
  7. Kloosterman W, Guryev V, Van Roosmalen M, Duran K, de Bruijn E, Bakker S, et al. Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum Mol Genet. 2011;20:1916-24 pubmed publisher
    ..We conclude that a similar mechanism may also drive the formation of de novo structural variation in the germline...
  8. Asaithamby A, Hu B, Delgado O, Ding L, Story M, Minna J, et al. Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture. Nucleic Acids Res. 2011;39:5474-88 pubmed publisher
    ..Our data suggest that downregulation of multiple DNA repair pathway genes in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis...
  9. Letessier A, Millot G, Koundrioukoff S, Lachages A, Vogt N, Hansen R, et al. Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. Nature. 2011;470:120-3 pubmed publisher
    ..Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates...

More Information

Publications62

  1. Schwartz J, Plotnik D, Slovic J, Li T, Racelis M, Deeg H, et al. Tp53 codon-72 polymorphisms identify different radiation sensitivities to g2-chromosome breakage in human lymphoblast cells. Environ Mol Mutagen. 2011;52:77-80 pubmed publisher
    ..Distinguishing the effect of TP53 codon-72 variations from other modifiers of G2-chromosome radiosensitivity might aid in identifying new markers of cancer risk...
  2. Martinez A C, van Wely K. Are aneuploidy and chromosome breakage caused by a CINgle mechanism?. Cell Cycle. 2010;9:2275-80 pubmed
    ..Since a poorly controlled spindle can cause merotelic attachments, kinetochore distortion, and subsequent chromosome breakage, spindle defects can generate the sticky ends necessary to start a breakage-fusion-bridge cycle...
  3. Toledo L, Murga M, Zur R, Soria R, Rodriguez A, Martinez S, et al. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol. 2011;18:721-7 pubmed publisher
  4. Pobiega S, Marcand S. Dicentric breakage at telomere fusions. Genes Dev. 2010;24:720-33 pubmed publisher
    ..This unforeseen result suggests a rescue pathway able to process telomere fusions and to back up NHEJ inhibition at telomeres...
  5. Feng W, Bachant J, Collingwood D, Raghuraman M, Brewer B. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress. Genetics. 2009;183:1249-60 pubmed publisher
    ..Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression...
  6. Rey L, Sidorova J, Puget N, Boudsocq F, Biard D, Monnat R, et al. Human DNA polymerase eta is required for common fragile site stability during unperturbed DNA replication. Mol Cell Biol. 2009;29:3344-54 pubmed publisher
  7. Smith C, Lam A, Symington L. Aberrant double-strand break repair resulting in half crossovers in mutants defective for Rad51 or the DNA polymerase delta complex. Mol Cell Biol. 2009;29:1432-41 pubmed publisher
    ..Thus, the BIR defect observed for rad51 mutants is due to strand invasion failure, whereas the Pol delta complex mutants are proficient for strand invasion but unable to complete extensive tracts of recombination-initiated DNA synthesis...
  8. Hashash N, Johnson A, Cha R. Topoisomerase II- and condensin-dependent breakage of MEC1ATR-sensitive fragile sites occurs independently of spindle tension, anaphase, or cytokinesis. PLoS Genet. 2012;8:e1002978 pubmed publisher
    Fragile sites are loci of recurrent chromosome breakage in the genome. They are found in organisms ranging from bacteria to humans and are implicated in genome instability, evolution, and cancer...
  9. Girirajan S, Chen L, Graves T, Marques Bonet T, Ventura M, Fronick C, et al. Sequencing human-gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sites. Genome Res. 2009;19:178-90 pubmed publisher
  10. Gagos S, Chiourea M, Christodoulidou A, Apostolou E, Raftopoulou C, Deustch S, et al. Pericentromeric instability and spontaneous emergence of human neoacrocentric and minute chromosomes in the alternative pathway of telomere lengthening. Cancer Res. 2008;68:8146-55 pubmed publisher
    ..These observations are important in understanding the global genomic instability that characterizes most human advanced malignancies...
  11. Lemaitre C, Tannier E, Gautier C, Sagot M. Precise detection of rearrangement breakpoints in mammalian chromosomes. BMC Bioinformatics. 2008;9:286 pubmed publisher
    ..Contrary to current methods which search for synteny blocks and simply return what remains in the genome as breakpoints, we propose to go further and to investigate the breakpoints themselves in order to refine them...
  12. Russell B, Bhattacharyya S, Keirsey J, Sandy A, Grierson P, Perchiniak E, et al. Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha. Cancer Res. 2011;71:561-71 pubmed publisher
    ..Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells...
  13. Larkin D, Pape G, Donthu R, Auvil L, Welge M, Lewin H. Breakpoint regions and homologous synteny blocks in chromosomes have different evolutionary histories. Genome Res. 2009;19:770-7 pubmed publisher
    ..These results demonstrate that chromosome breakage in evolution is nonrandom and that HSBs and EBRs are evolving in distinctly different ways...
  14. Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J, et al. New insights to the MLL recombinome of acute leukemias. Leukemia. 2009;23:1490-9 pubmed publisher
    ..Moreover, we describe for the first time the genetic network of reciprocal MLL gene fusions deriving from complex rearrangements...
  15. Asaithamby A, Hu B, Chen D. Unrepaired clustered DNA lesions induce chromosome breakage in human cells. Proc Natl Acad Sci U S A. 2011;108:8293-8 pubmed publisher
    ..Difficulties associated with clustered DNA damage repair and checkpoint release before the completion of clustered DNA damage repair appear to promote genome instability that may lead to carcinogenesis...
  16. Liu P, Erez A, Nagamani S, Dhar S, Kołodziejska K, Dharmadhikari A, et al. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell. 2011;146:889-903 pubmed publisher
    ..The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle...
  17. Debatisse M, Malfoy B. Gene amplification mechanisms. Adv Exp Med Biol. 2005;570:343-61 pubmed publisher
  18. Deckbar D, Stiff T, Koch B, Reis C, Lobrich M, Jeggo P. The limitations of the G1-S checkpoint. Cancer Res. 2010;70:4412-21 pubmed publisher
  19. Crasta K, Ganem N, Dagher R, Lantermann A, Ivanova E, Pan Y, et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature. 2012;482:53-8 pubmed publisher
    ..Pulverization of chromosomes in micronuclei may also be one explanation for 'chromothripsis' in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement...
  20. Bennardo N, Cheng A, Huang N, Stark J. Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet. 2008;4:e1000110 pubmed publisher
    ..However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy...
  21. Fantauzzo K, Tadin Strapps M, You Y, Mentzer S, Baumeister F, Cianfarani S, et al. A position effect on TRPS1 is associated with Ambras syndrome in humans and the Koala phenotype in mice. Hum Mol Genet. 2008;17:3539-51 pubmed publisher
    ..Collectively, these results describe a position effect that downregulates TRPS1 expression as the probable cause of hypertrichosis in AS in humans and the Koa phenotype in mice...
  22. Xanthopoulou L, Ghevaria H, Mantzouratou A, Serhal P, Doshi A, Delhanty J. Chromosome breakage in human preimplantation embryos from carriers of structural chromosomal abnormalities in relation to fragile sites, maternal age, and poor sperm factors. Cytogenet Genome Res. 2012;136:21-9 pubmed publisher
    b>Chromosome breakage is a fairly widespread phenomenon in preimplantation embryos affecting at least 10% of day 3 cleavage stage embryos. It may be detected during preimplantation genetic diagnosis (PGD)...
  23. Sinclair P, Parker H, An Q, Rand V, Ensor H, Harrison C, et al. Analysis of a breakpoint cluster reveals insight into the mechanism of intrachromosomal amplification in a lymphoid malignancy. Hum Mol Genet. 2011;20:2591-602 pubmed publisher
    ..These findings provide insight into potential mechanisms involved in the formation of iAMP21...
  24. Anand R, Shah K, Niu H, Sung P, Mirkin S, Freudenreich C. Overcoming natural replication barriers: differential helicase requirements. Nucleic Acids Res. 2012;40:1091-105 pubmed publisher
    ..Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures...
  25. Lin I, Chao J, Yao M. An essential role for the DNA breakage-repair protein Ku80 in programmed DNA rearrangements in Tetrahymena thermophila. Mol Biol Cell. 2012;23:2213-25 pubmed publisher
    ..Moreover, chromosome breakage or de novo telomere addition was affected...
  26. Schvartzman J, Sotillo R, Benezra R. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer. 2010;10:102-15 pubmed publisher
    ..How chromosome instability (CIN) arises in tumours and what consequences it has are still, however, hotly debated issues. Here we review the recent literature with an emphasis on models that recapitulate observations from human disease...
  27. Bennardo N, Gunn A, Cheng A, Hasty P, Stark J. Limiting the persistence of a chromosome break diminishes its mutagenic potential. PLoS Genet. 2009;5:e1000683 pubmed publisher
    ..Furthermore, we find that individual genetic factors play distinct roles during repair of non-cohesive DSB ends that are generated via co-expression of I-SceI with Trex2...
  28. Lee K, Zhang Y, Lee S. Saccharomyces cerevisiae ATM orthologue suppresses break-induced chromosome translocations. Nature. 2008;454:543-6 pubmed publisher
  29. Sharp A, Hansen S, Selzer R, Cheng Z, Regan R, Hurst J, et al. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet. 2006;38:1038-42 pubmed
    ..In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions...
  30. Schibler L, Roig A, Mahé M, Laurent P, Hayes H, Rodolphe F, et al. High-resolution comparative mapping among man, cattle and mouse suggests a role for repeat sequences in mammalian genome evolution. BMC Genomics. 2006;7:194 pubmed
    ..In this work, we have explored the presence of interspersed repeats in regions of chromosomal rearrangements, using an updated high-resolution integrated comparative map among cattle, man and mouse...
  31. Kurahashi H, Inagaki H, Ohye T, Kogo H, Kato T, Emanuel B. Palindrome-mediated chromosomal translocations in humans. DNA Repair (Amst). 2006;5:1136-45 pubmed
    ..We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation...
  32. Debacker K, Winnepenninckx B, Ben Porat N, Fitzpatrick D, van Luijk R, Scheers S, et al. FRA18C: a new aphidicolin-inducible fragile site on chromosome 18q22, possibly associated with in vivo chromosome breakage. J Med Genet. 2007;44:347-52 pubmed
    ..The breakpoint region was highly enriched in AT-rich sequences. It is the first report of an aphidicolin-sensitive fragile site that coincides with an in vivo chromosome truncation in the progeny...
  33. Yu T, Ye H, Sun W, Li K, Chen Z, Jacobs S, et al. A forward-backward fragment assembling algorithm for the identification of genomic amplification and deletion breakpoints using high-density single nucleotide polymorphism (SNP) array. BMC Bioinformatics. 2007;8:145 pubmed
    ..To accurately identify small segments of CNA from SNP array data, segmentation methods that are sensitive to CNA while resistant to noise are required...
  34. Yamauchi Y, Ajduk A, Riel J, Ward M. Ejaculated and epididymal mouse spermatozoa are different in their susceptibility to nuclease-dependent DNA damage and in their nuclease activity. Biol Reprod. 2007;77:636-47 pubmed
    ..This nuclease activity was detected both in the sperm-free fraction of preparations and isolated sperm...
  35. Darai Ramqvist E, Sandlund A, Muller S, Klein G, Imreh S, Kost Alimova M. Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions. Genome Res. 2008;18:370-9 pubmed publisher
  36. Weksberg R, Stachon A, Squire J, Moldovan L, Bayani J, Meyn S, et al. Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome. Hum Genet. 2007;120:837-45 pubmed
    ..Further studies are needed to elucidate the molecular basis of schizophrenia and clinical heterogeneity in 22q11DS...
  37. Ma J, Zhang L, Suh B, Raney B, Burhans R, Kent W, et al. Reconstructing contiguous regions of an ancestral genome. Genome Res. 2006;16:1557-65 pubmed
    ..Our methods were developed as part of a project to reconstruct the genome sequence of the last ancestor of human, dogs, and most other placental mammals...
  38. Gribble S, Kalaitzopoulos D, Burford D, Prigmore E, Selzer R, Ng B, et al. Ultra-high resolution array painting facilitates breakpoint sequencing. J Med Genet. 2007;44:51-8 pubmed
    ..To describe a considerably advanced method of array painting, which allows the rapid, ultra-high resolution mapping of translocation breakpoints such that rearrangement junction fragments can be amplified directly and sequenced...
  39. Kohno T, Yokota J. Molecular processes of chromosome 9p21 deletions causing inactivation of the p16 tumor suppressor gene in human cancer: deduction from structural analysis of breakpoints for deletions. DNA Repair (Amst). 2006;5:1273-81 pubmed
    ..Further structural analysis of other hot spots of chromosomal DNA breaks as well as the evaluation of the activity and specificity of NHEJ in human cells will elucidate the mechanisms of chromosome interstitial deletions in human cells...
  40. Selvarajah S, Yoshimoto M, Park P, Maire G, Paderova J, Bayani J, et al. The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma. Chromosoma. 2006;115:459-67 pubmed
  41. Zhang H, Freudenreich C. An AT-rich sequence in human common fragile site FRA16D causes fork stalling and chromosome breakage in S. cerevisiae. Mol Cell. 2007;27:367-79 pubmed
    ..Our data suggest that the FRA16D Flex1 sequence causes increased chromosome breakage by forming secondary structures that stall replication fork progression.
  42. Lupski J. Genome structural variation and sporadic disease traits. Nat Genet. 2006;38:974-6 pubmed
  43. Johnston J, Walker R, Davis S, Facio F, Turner J, Bick D, et al. Zoom-in comparative genomic hybridisation arrays for the characterisation of variable breakpoint contiguous gene syndromes. J Med Genet. 2007;44:e59 pubmed
    ..We suggest that high-density CGH array analysis should replace FISH analysis for assessment of deletions and duplications in patients with contiguous gene syndromes caused by variable deletions...
  44. Smith D, McAvoy S, Zhu Y, Perez D. Large common fragile site genes and cancer. Semin Cancer Biol. 2007;17:31-41 pubmed
    ..In this review we will discuss the large common fragile site genes that have been identified to date, and the role that these genes appear to play both in cellular responses to stress and in the development of cancer...
  45. Meyer C, Burmeister T, Strehl S, Schneider B, Hubert D, Zach O, et al. Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(q23;p13.3) leukemia. Leukemia. 2007;21:588-90 pubmed
  46. Ranz J, Maurin D, Chan Y, von Grotthuss M, Hillier L, Roote J, et al. Principles of genome evolution in the Drosophila melanogaster species group. PLoS Biol. 2007;5:e152 pubmed
    ..Outgroup analysis also revealed evidence for widespread breakpoint recycling. Lastly, we have found that expression domains in D. melanogaster may be disrupted in D. yakuba, bringing into question their potential adaptive significance...
  47. Freudenreich C. Chromosome fragility: molecular mechanisms and cellular consequences. Front Biosci. 2007;12:4911-24 pubmed
    ..An understanding of these events will provide insight into the generation of cancer, since deletions and rearrangements at human common fragile sites and associated tumor suppressor genes are an early event in tumorigenesis...
  48. Makoff A, Flomen R. Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi, Angelman, and inv dup(15) syndromes. Genome Biol. 2007;8:R114 pubmed
    ..We have investigated this region by conducting a detailed examination of the sequenced genomic clones in the public database, focusing on clones from the RP11 library that originates from one individual...
  49. Gordon L, Yang S, Tran Gyamfi M, Baggott D, Christensen M, Hamilton A, et al. Comparative analysis of chicken chromosome 28 provides new clues to the evolutionary fragility of gene-rich vertebrate regions. Genome Res. 2007;17:1603-13 pubmed
  50. Liu Y, Taverna S, Muratore T, Shabanowitz J, Hunt D, Allis C. RNAi-dependent H3K27 methylation is required for heterochromatin formation and DNA elimination in Tetrahymena. Genes Dev. 2007;21:1530-45 pubmed
    ..These studies provide a framework for an RNAi-dependent, Polycomb group protein-mediated heterochromatin formation pathway in Tetrahymena and underscore the connection between the two highly conserved machineries in eukaryotes...
  51. Yan C, Boboila C, Souza E, Franco S, Hickernell T, Murphy M, et al. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature. 2007;449:478-82 pubmed
    ..In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations...
  52. Yamauchi Y, Doe B, Ajduk A, Ward M. Genomic DNA damage in mouse transgenesis. Biol Reprod. 2007;77:803-12 pubmed
    ..The present study demonstrates that DNA damage occurs after both the microinjection of pronuclei and ICSI-mediated transgenesis, albeit through different mechanisms...
  53. Haber J. Chromosome breakage and repair. Genetics. 2006;173:1181-5 pubmed