genomic instability

Summary

Summary: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.

Top Publications

  1. Wang J, Chen J, Gong Z. TopBP1 controls BLM protein level to maintain genome stability. Mol Cell. 2013;52:667-78 pubmed publisher
    ..Altogether, these data suggest that, although BLM is downregulated in G1 phase in order to promote NHEJ-mediated DNA repair, it is stabilized by TopBP1 in S phase cells in order to suppress SCE and thereby prevent genomic instability.
  2. Saini N, Ramakrishnan S, Elango R, Ayyar S, Zhang Y, Deem A, et al. Migrating bubble during break-induced replication drives conservative DNA synthesis. Nature. 2013;502:389-92 pubmed publisher
    ..We propose that the BIR mode of synthesis presents a powerful mechanism that can initiate bursts of genetic instability in eukaryotes, including humans. ..
  3. McKinnon P. Maintaining genome stability in the nervous system. Nat Neurosci. 2013;16:1523-9 pubmed publisher
    ..Understanding how DNA damage signaling pathways promote neural development and preserve homeostasis is essential for understanding fundamental brain function. ..
  4. Akagi K, Li J, Broutian T, Padilla Nash H, Xiao W, Jiang B, et al. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2014;24:185-99 pubmed publisher
    b>Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV)...
  5. Castellano Pozo M, Santos Pereira J, Rondon A, Barroso S, Andújar E, Pérez Alegre M, et al. R loops are linked to histone H3 S10 phosphorylation and chromatin condensation. Mol Cell. 2013;52:583-90 pubmed publisher
    ..Such histone modifications were also observed in R-loop-accumulating Caenorhabditis elegans and HeLa cells. We therefore provide a role of RNA in chromatin structure essential to understand how R loops modulate genome dynamics. ..
  6. Savage K, Matchett K, Barros E, Cooper K, Irwin G, Gorski J, et al. BRCA1 deficiency exacerbates estrogen-induced DNA damage and genomic instability. Cancer Res. 2014;74:2773-2784 pubmed publisher
    ..breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing ..
  7. Wallace N, Robinson K, Galloway D. Beta human papillomavirus E6 expression inhibits stabilization of p53 and increases tolerance of genomic instability. J Virol. 2014;88:6112-27 pubmed publisher
    ..These data support the hypothesis that ?-HPV infections may promote tumorigenesis via genome destabilization...
  8. Bhatia V, Barroso S, García Rubio M, Tumini E, Herrera Moyano E, Aguilera A. BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2. Nature. 2014;511:362-5 pubmed publisher
    ..This link between BRCA2 and RNA-mediated genome instability indicates that R-loops may be a chief source of replication stress and cancer-associated instability. ..
  9. Toiber D, Erdel F, Bouazoune K, Silberman D, Zhong L, Mulligan P, et al. SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Mol Cell. 2013;51:454-68 pubmed publisher
    ..We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage. ..

More Information

Publications61

  1. Germann S, Schramke V, Pedersen R, Gallina I, Eckert Boulet N, Oestergaard V, et al. TopBP1/Dpb11 binds DNA anaphase bridges to prevent genome instability. J Cell Biol. 2014;204:45-59 pubmed publisher
    ..In conclusion, we propose that TopBP1/Dpb11 prevents accumulation of anaphase bridges via stimulation of the Mec1/ATR kinase and suppression of homologous recombination...
  2. Køhler J, Jørgensen M, Beinoraité G, Thorsen M, Thon G. Concerted action of the ubiquitin-fusion degradation protein 1 (Ufd1) and Sumo-targeted ubiquitin ligases (STUbLs) in the DNA-damage response. PLoS ONE. 2013;8:e80442 pubmed publisher
    ..Broader functional relationships between Ufd1 and STUbLs conceivably affect numerous cellular processes beyond the DDR...
  3. Puccini J, Shalini S, Voss A, Gatei M, Wilson C, Hiwase D, et al. Loss of caspase-2 augments lymphomagenesis and enhances genomic instability in Atm-deficient mice. Proc Natl Acad Sci U S A. 2013;110:19920-5 pubmed publisher
  4. Albuquerque C, Wang G, Lee N, Kolodner R, Putnam C, Zhou H. Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements. PLoS Genet. 2013;9:e1003670 pubmed publisher
    ..Thus, distinct SUMO ligases work in concert with Esc2 and Slx5-Slx8 to control substrate specificity and sumoylation homeostasis to prevent GCRs. ..
  5. Vincent Salomon A, Benhamo V, Gravier E, Rigaill G, Gruel N, Robin S, et al. Genomic instability: a stronger prognostic marker than proliferation for early stage luminal breast carcinomas. PLoS ONE. 2013;8:e76496 pubmed publisher
    ..The accurate prognosis definition to tailor treatment for early luminal invasive breast carcinoma patients remains challenging...
  6. Jain A, Bacolla A, Del Mundo I, Zhao J, Wang G, Vasquez K. DHX9 helicase is involved in preventing genomic instability induced by alternatively structured DNA in human cells. Nucleic Acids Res. 2013;41:10345-57 pubmed publisher
    ..e. non-B) DNA structures in the human genome have been implicated in stimulating genomic instability. Previously, we found that a naturally occurring intra-molecular triplex (H-DNA) caused genetic instability ..
  7. Sriramachandran A, Dohmen R. SUMO-targeted ubiquitin ligases. Biochim Biophys Acta. 2014;1843:75-85 pubmed publisher
    ..This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. ..
  8. Beck H, Nähse Kumpf V, Larsen M, O Hanlon K, Patzke S, Holmberg C, et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol Cell Biol. 2012;32:4226-36 pubmed
  9. Jiang J, Lv W, Ye X, Wang L, Zhang M, Yang H, et al. Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation. Cell Res. 2013;23:92-106 pubmed publisher
    ..Our findings provide the first demonstration that maintaining genomic stability during reprogramming promotes the generation of high quality iPS cells...
  10. Yamtich J, Nemec A, Keh A, Sweasy J. A germline polymorphism of DNA polymerase beta induces genomic instability and cellular transformation. PLoS Genet. 2012;8:e1003052 pubmed publisher
    ..Our results suggest that people who carry the rs3136797 germline SNP may be at an increased risk for cancer susceptibility...
  11. Saldivar J, Miuma S, Bene J, Hosseini S, Shibata H, Sun J, et al. Initiation of genome instability and preneoplastic processes through loss of Fhit expression. PLoS Genet. 2012;8:e1003077 pubmed publisher
    b>Genomic instability drives tumorigenesis, but how it is initiated in sporadic neoplasias is unknown. In early preneoplasias, alterations at chromosome fragile sites arise due to DNA replication stress...
  12. Bochman M, Paeschke K, Zakian V. DNA secondary structures: stability and function of G-quadruplex structures. Nat Rev Genet. 2012;13:770-80 pubmed publisher
    ..This Review focuses on emerging evidence relating to the characteristics of G-quadruplex structures and the possible influence of such structures on genomic stability and cellular processes, such as transcription...
  13. Bhattacharjee P, Banerjee M, Giri A. Role of genomic instability in arsenic-induced carcinogenicity. A review. Environ Int. 2013;53:29-40 pubmed publisher
    ..Although unstable genome is a characteristic feature of cancer cells, the mechanisms leading to genomic instability in arsenic-induced carcinogenesis are poorly understood...
  14. Yang G, Mercado Uribe I, Multani A, Sen S, Shih I, Wong K, et al. RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis. Int J Cancer. 2013;133:275-85 pubmed publisher
    The oncogene RAS is known to induce genomic instability, leading to cancer development; the underlying mechanism, however, remains poorly understood...
  15. O Connor K, Dejsuphong D, Park E, Nicolae C, Kimmelman A, D Andrea A, et al. PARI overexpression promotes genomic instability and pancreatic tumorigenesis. Cancer Res. 2013;73:2529-39 pubmed publisher
    ..PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell-cycle ..
  16. Valdiglesias V, Giunta S, Fenech M, Neri M, Bonassi S. ?H2AX as a marker of DNA double strand breaks and genomic instability in human population studies. Mutat Res. 2013;753:24-40 pubmed publisher
    ..Failure to detect DSB and activate appropriate DNA damage responses can cause genomic instability, leading to tumorigenesis and possibly accelerated aging...
  17. Donigan K, Tuck D, Schulz V, Sweasy J. DNA polymerase ? variant Ile260Met generates global gene expression changes related to cellular transformation. Mutagenesis. 2012;27:683-91 pubmed publisher
    ..This suggests that the PPARG2 mutant may have played a role in driving cellular transformation. We conclude that PPARG induces cellular transformation by a mutational mechanism...
  18. Ying S, Minocherhomji S, Chan K, Palmai Pallag T, Chu W, Wass T, et al. MUS81 promotes common fragile site expression. Nat Cell Biol. 2013;15:1001-7 pubmed publisher
    ..Our findings challenge the prevailing view that CFS breakage is a nonspecific process that is detrimental to cells, and indicate that CFS cleavage actually promotes genome stability. ..
  19. Bunting S, Nussenzweig A. End-joining, translocations and cancer. Nat Rev Cancer. 2013;13:443-54 pubmed publisher
    ..The factors and pathways that promote translocations are becoming clearer, with non-homologous end-joining implicated as a key source of genomic rearrangements. ..
  20. Halaby M, Hakem A, Li L, El Ghamrasni S, Venkatesan S, Hande P, et al. Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis. PLoS Genet. 2013;9:e1003259 pubmed publisher
    ..In addition, Rnf8(-/-)p53(-/-) mice had increased levels of genomic instability and a remarkably elevated tumor incidence compared to either Rnf8(-/-) or p53(-/-) mice...
  21. Bhat A, Andersen P, Qin Z, Xiao W. Rev3, the catalytic subunit of Pol?, is required for maintaining fragile site stability in human cells. Nucleic Acids Res. 2013;41:2328-39 pubmed publisher
    ..The genomic instability induced by Rev3 depletion seems to be related to replication stress, as it is further enhanced on ..
  22. Barlow J, Faryabi R, Callén E, Wong N, Malhowski A, Chen H, et al. Identification of early replicating fragile sites that contribute to genome instability. Cell. 2013;152:620-32 pubmed publisher
    ..Moreover, greater than 50% of recurrent amplifications/deletions in human diffuse large B cell lymphoma map to ERFSs. In summary, we have identified a source of spontaneous DNA lesions that drives instability at preferred genomic sites. ..
  23. Bolton Gillespie E, Schemionek M, Klein H, Flis S, Hoser G, Lange T, et al. Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells. Blood. 2013;121:4175-83 pubmed publisher
    b>Genomic instability is a hallmark of chronic myeloid leukemia in chronic phase (CML-CP) resulting in BCR-ABL1 mutations encoding resistance to tyrosine kinase inhibitors (TKIs) and/or additional chromosomal aberrations leading to disease ..
  24. Bonnet F, Guedj M, Jones N, Sfar S, Brouste V, Elarouci N, et al. An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis. BMC Med Genomics. 2012;5:54 pubmed publisher
    ..Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical ..
  25. Caldon C, Sergio C, Burgess A, Deans A, Sutherland R, Musgrove E. Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1. Cell Cycle. 2013;12:606-17 pubmed publisher
    ..of DNA replication, and deregulation of its periodic expression leads to mitotic delay associated with genomic instability. Since it is not known whether the closely related protein cyclin E2 shares these properties, we ..
  26. Vriend L, De Witt Hamer P, Van Noorden C, Wurdinger T. WEE1 inhibition and genomic instability in cancer. Biochim Biophys Acta. 2013;1836:227-35 pubmed publisher
    One of the hallmarks of cancer is genomic instability controlled by cell cycle checkpoints...
  27. Gonzalez Vasconcellos I, Anastasov N, Sanli Bonazzi B, Klymenko O, Atkinson M, Rosemann M. Rb1 haploinsufficiency promotes telomere attrition and radiation-induced genomic instability. Cancer Res. 2013;73:4247-55 pubmed publisher
    ..predispose to both sporadic and radiation-induced osteosarcoma, tumors characterized by high levels of genomic instability, and activation of alternative lengthening of telomeres...
  28. Mokrani Benhelli H, Gaillard L, Biasutto P, Le Guen T, Touzot F, Vasquez N, et al. Primary microcephaly, impaired DNA replication, and genomic instability caused by compound heterozygous ATR mutations. Hum Mutat. 2013;34:374-84 pubmed publisher
    ..alteration of several DNA replication parameters in patient's cells and FISH analyses highlighted the genomic instability caused by ATR deficiency...
  29. Price B, D Andrea A. Chromatin remodeling at DNA double-strand breaks. Cell. 2013;152:1344-54 pubmed publisher
  30. Muñoz Galvan S, Jimeno S, Rothstein R, Aguilera A. Histone H3K56 acetylation, Rad52, and non-DNA repair factors control double-strand break repair choice with the sister chromatid. PLoS Genet. 2013;9:e1003237 pubmed publisher
    ..A dysfunction can lead to genome instability as manifested by high levels of homolog recombination and DSB accumulation...
  31. Maeda J, Yurkon C, Fujisawa H, Kaneko M, Genet S, Roybal E, et al. Genomic instability and telomere fusion of canine osteosarcoma cells. PLoS ONE. 2012;7:e43355 pubmed publisher
    ..Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA...
  32. Tivey H, Brook A, Rokicki M, Kipling D, Davis T. p38 (MAPK) stress signalling in replicative senescence in fibroblasts from progeroid and genomic instability syndromes. Biogerontology. 2013;14:47-62 pubmed publisher
    ..This suggests that stress-induced premature cellular senescence via p38 activation is restricted to a small subset of progeroid syndromes...
  33. 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...
  34. Guidi R, Guerra L, Levi L, Stenerlow B, Fox J, Josenhans C, et al. Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response. Cell Microbiol. 2013;15:98-113 pubmed publisher
    ..that chronic exposure to the genotoxin cytolethal distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and acquisition of phenotypic properties of malignancy in fibroblasts and colon epithelial cells...
  35. Wilson M, Harreman M, Svejstrup J. Ubiquitylation and degradation of elongating RNA polymerase II: the last resort. Biochim Biophys Acta. 2013;1829:151-7 pubmed publisher
    ..In this review, we describe the mechanisms and factors responsible for the last resort mechanism of transcriptional elongation. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation...
  36. Popuri V, Huang J, Ramamoorthy M, Tadokoro T, Croteau D, Bohr V. RECQL5 plays co-operative and complementary roles with WRN syndrome helicase. Nucleic Acids Res. 2013;41:881-99 pubmed publisher
    ..Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death...
  37. Zhang Y, Shishkin A, Nishida Y, Marcinkowski Desmond D, Saini N, Volkov K, et al. Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividing and nondividing yeast cells. Mol Cell. 2012;48:254-65 pubmed publisher
    ..We propose that similar mechanisms can mediate detrimental metabolism of GAA/TTC tracts in human cells...
  38. Beggs A, Domingo E, Abulafi M, Hodgson S, Tomlinson I. A study of genomic instability in early preneoplastic colonic lesions. Oncogene. 2013;32:5333-7 pubmed publisher
    ..We aimed to carry out an analysis of gland level genomic instability for MSI and promoter methylation...
  39. Chene G, Tchirkov A, Pierre Eymard E, Dauplat J, Raoelfils I, Cayre A, et al. Early telomere shortening and genomic instability in tubo-ovarian preneoplastic lesions. Clin Cancer Res. 2013;19:2873-82 pubmed publisher
    ..We investigated the level of telomere shortening and genomic instability in early and preinvasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC), and tubo-..
  40. Szakal B, Branzei D. Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and deleterious crossover. EMBO J. 2013;32:1155-67 pubmed publisher
  41. Clark V, Erson Omay E, Serin A, Yin J, Cotney J, Ozduman K, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013;339:1077-80 pubmed publisher
    ..In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres...
  42. Rudolph C, Upton A, Stockum A, Nieduszynski C, Lloyd R. Avoiding chromosome pathology when replication forks collide. Nature. 2013;500:608-11 pubmed publisher
    ..The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome. ..
  43. Li Z, Owonikoko T, Sun S, Ramalingam S, Doetsch P, Xiao Z, et al. c-Myc suppression of DNA double-strand break repair. Neoplasia. 2012;14:1190-202 pubmed
    ..of DSB repair and V(D)J recombination may occur through inhibition of the nonhomologous end-joining pathway, which provides insight into the mechanism of c-Myc in the development of tumors through promotion of genomic instability.
  44. Helmrich A, Ballarino M, Nudler E, Tora L. Transcription-replication encounters, consequences and genomic instability. Nat Struct Mol Biol. 2013;20:412-8 pubmed publisher
    ..DNA-polymerase complexes may result in clashes of those machineries on the DNA template and thus increase genomic instability. In addition, we summarize strategies evolved in bacteria and eukaryotes to minimize the consequences of ..
  45. Lin Y, Wilson J. Nucleotide excision repair, mismatch repair, and R-loops modulate convergent transcription-induced cell death and repeat instability. PLoS ONE. 2012;7:e46807 pubmed publisher
    ..These observations link the mechanisms of convergent transcription-induced repeat instability and convergent transcription-induced cell death, suggesting that a common structure may trigger both outcomes...
  46. Slupianek A, Falinski R, Znojek P, Stoklosa T, Flis S, Doneddu V, et al. BCR-ABL1 kinase inhibits uracil DNA glycosylase UNG2 to enhance oxidative DNA damage and stimulate genomic instability. Leukemia. 2013;27:629-34 pubmed publisher
  47. Lund R, Närvä E, Lahesmaa R. Genetic and epigenetic stability of human pluripotent stem cells. Nat Rev Genet. 2012;13:732-44 pubmed publisher
    ..In this Review, we summarize the current knowledge of the genomic and epigenomic stability of pluripotent human cells and the implications for stem cell research...
  48. Gupta A, Hunt C, Pandita R, Pae J, Komal K, Singh M, et al. T-cell-specific deletion of Mof blocks their differentiation and results in genomic instability in mice. Mutagenesis. 2013;28:263-70 pubmed publisher
    ..PHA) stimulation, whereas LPS-stimulated B cells from Mof(F/F)/Lck-Cre(+) mice demonstrated spontaneous genomic instability. Mice with T-cell-specific loss of MOF had shorter lifespans and decreased survival following irradiation ..
  49. Alt F, Zhang Y, Meng F, Guo C, Schwer B. Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell. 2013;152:417-29 pubmed publisher
    ..We also discuss recent work that provides new insights into DSB repair pathways and the influences of three-dimensional genome organization on physiological processes and cancer genomes...
  50. Karotki A, Baverstock K. What mechanisms/processes underlie radiation-induced genomic instability?. Cell Mol Life Sci. 2012;69:3351-60 pubmed publisher
    Radiation-induced genomic instability is a modification of the cell genome found in the progeny of irradiated somatic and germ cells but that is not confined on the initial radiation-induced damage and may occur de novo many generations ..
  51. Croteau D, Singh D, Hoh Ferrarelli L, Lu H, Bohr V. RECQL4 in genomic instability and aging. Trends Genet. 2012;28:624-31 pubmed publisher
    ..In addition, new protein partners are emerging, implicating RECQL4 in novel processes. Here, we describe these recent findings which place RECQL4 at the crossroads of genomic instability and aging processes.
  52. Kim J, Kim W, Park C. Epstein-Barr virus latent membrane protein 1 increases genomic instability through Egr-1-mediated up-regulation of activation-induced cytidine deaminase in B-cell lymphoma. Leuk Lymphoma. 2013;54:2035-40 pubmed publisher
    ..Collectively, LMP1 induces AID up-regulation and genomic instability via Egr-1...