aphidicolin

Summary

Summary: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.

Top Publications

  1. Liu J, Kuo S, Melendy T. Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents. Mutat Res. 2003;532:215-26 pubmed
    ..of cultured mammalian cells with agents that either inhibit DNA polymerase activity (hydroxyurea (HU) or aphidicolin) or selectively induce S-phase DNA damage responses (the DNA alkylating agents, methyl methanesulfonate (MMS) ..
  2. Shechter D, Costanzo V, Gautier J. Regulation of DNA replication by ATR: signaling in response to DNA intermediates. DNA Repair (Amst). 2004;3:901-8 pubmed
    ..fork stalling, including damage caused by ultraviolet irradiation, hyperoxia, and replication inhibitors like aphidicolin and hydroxyurea...
  3. Kurose A, Tanaka T, Huang X, Traganos F, Dai W, Darzynkiewicz Z. Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis. Cytometry A. 2006;69:212-21 pubmed
    ..b>Aphidicolin (APH), an inhibitor of alpha-like DNA polymerases, was also reported to cause DNA damage, but the evidence for ..
  4. Hammond E, Green S, Giaccia A. Comparison of hypoxia-induced replication arrest with hydroxyurea and aphidicolin-induced arrest. Mutat Res. 2003;532:205-13 pubmed
    ..The drugs aphidicolin and hydroxyurea both induce rapid replication arrest and have been used throughout the literature to study the ..
  5. Spadari S, Pedrali Noy G, Falaschi M, Ciarrocchi G. Control of DNA replication and cell proliferation in eukaryotes by aphidicolin. Toxicol Pathol. 1984;12:143-8 pubmed
    The mycotoxin aphidicolin specifically inhibits nuclear DNA synthesis in eukaryotic cells by intereacting with the replicative DNA polymerase alpha...
  6. Sasakawa N, Fukui T, Waga S. Accumulation of FFA-1, the Xenopus homolog of Werner helicase, and DNA polymerase delta on chromatin in response to replication fork arrest. J Biochem. 2006;140:95-103 pubmed
    ..Thus, WRN-specific, distinct processes can be reproduced in the in vitro system in egg extracts, and this system is useful for biochemical analysis of WRN functions during DNA metabolism. ..
  7. Casper A, Durkin S, Arlt M, Glover T. Chromosomal instability at common fragile sites in Seckel syndrome. Am J Hum Genet. 2004;75:654-60 pubmed
    ..chromosomal instability, particularly at fragile sites, in SCKL1-affected patient cells after treatment with aphidicolin, an inhibitor of DNA polymerase alpha and other polymerases...
  8. Yanow S, Gold D, Yoo H, Dunphy W. Xenopus Drf1, a regulator of Cdc7, displays checkpoint-dependent accumulation on chromatin during an S-phase arrest. J Biol Chem. 2003;278:41083-92 pubmed
    ..Nonetheless, Drf1 displays highly regulated binding to replicating chromatin. Treatment of egg extracts with aphidicolin results in a substantial accumulation of Drf1 on chromatin...
  9. Rybaczek D, Bodys A, Maszewski J. H2AX foci in late S/G2- and M-phase cells after hydroxyurea- and aphidicolin-induced DNA replication stress in Vicia. Histochem Cell Biol. 2007;128:227-41 pubmed
    ..using alpha-phospho-H2AX antibodies shows that hydroxyurea (HU), an inhibitor of ribonucleotide reductase, and aphidicolin (APH), an inhibitor of DNA-polymerases alpha and delta, may promote formation of phospho-H2AX foci in late S/G2-..

More Information

Publications75

  1. Madine M, Khoo C, Mills A, Musahl C, Laskey R. The nuclear envelope prevents reinitiation of replication by regulating the binding of MCM3 to chromatin in Xenopus egg extracts. Curr Biol. 1995;5:1270-9 pubmed
    ..Based on these results we present a two-stage model for replication licensing. ..
  2. Arlt M, MULLE J, Schaibley V, Ragland R, Durkin S, Warren S, et al. Replication stress induces genome-wide copy number changes in human cells that resemble polymorphic and pathogenic variants. Am J Hum Genet. 2009;84:339-50 pubmed publisher
    ..Here we show that aphidicolin-induced replication stress in normal human cells leads to a high frequency of CNCs of tens to thousands of ..
  3. Sakamoto S, Nishikawa K, Heo S, Goto M, Furuichi Y, Shimamoto A. Werner helicase relocates into nuclear foci in response to DNA damaging agents and co-localizes with RPA and Rad51. Genes Cells. 2001;6:421-30 pubmed
    ..The presence of aphidicolin inhibited CPT-induced WRNp foci strongly but not bleomycin-induced foci...
  4. Lyons D, Pogoda H, Voas M, Woods I, Diamond B, Nix R, et al. erbb3 and erbb2 are essential for schwann cell migration and myelination in zebrafish. Curr Biol. 2005;15:513-24 pubmed
    ..These results provide in vivo evidence that Neuregulin-ErbB signaling is essential for directed Schwann cell migration and demonstrate that this pathway is also required for the onset of myelination in postmigratory Schwann cells. ..
  5. Toyomasu T, Nakaminami K, Toshima H, Mie T, Watanabe K, Ito H, et al. Cloning of a gene cluster responsible for the biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA polymerase alpha. Biosci Biotechnol Biochem. 2004;68:146-52 pubmed
    The fungal diterpene, aphidicolin, is a well-known specific inhibitor of DNA polymerase alpha. Terpenoids are an important class of natural products...
  6. Ghoshal K, Datta J, Majumder S, Bai S, Kutay H, Motiwala T, et al. 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol. 2005;25:4727-41 pubmed
    ..These results demonstrate a unique mechanism for the selective degradation of DNMT1, the maintenance DNA methyltransferase, by well-known DNA-hypomethylating agents. ..
  7. Hekmat Nejad M, You Z, Yee M, Newport J, Cimprich K. Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint. Curr Biol. 2000;10:1565-73 pubmed
    ..of replication, dissociates from chromatin upon completion of replication, and accumulates in the presence of aphidicolin, an inhibitor of DNA replication...
  8. Saintigny Y, Delacote F, Vares G, Petitot F, Lambert S, Averbeck D, et al. Characterization of homologous recombination induced by replication inhibition in mammalian cells. EMBO J. 2001;20:3861-70 pubmed
    ..We propose that replication inhibition produces DSBs, which are first processed by the NHEJ; then, following DSB accumulation, RAD51 recombination can act. ..
  9. Zhang T, Dai J, Wu C, Gu X, Liu L, Wu Z, et al. Positive effects of treatment of donor cells with aphidicolin on the preimplantation development of somatic cell nuclear transfer embryos in Chinese Bama mini-pig (Sus Scrofa). Anim Sci J. 2012;83:103-10 pubmed publisher
    ..SCNT) procedures in mini-pigs, the present study was designed to examine the effects of donor cell types and aphidicolin (APC) treatment on in vitro development of reconstructed embryos...
  10. Speit G, Leibiger C, Kuehner S, Högel J. Further investigations on the modified comet assay for measuring aphidicolin-block nucleotide excision repair. Mutagenesis. 2013;28:145-51 pubmed publisher
    ..cells with benzo[a]pyrene diol epoxide (BPDE) in the presence or absence of the DNA polymerase inhibitor aphidicolin (APC) was developed (Vande Loock, K., Decordier, I., Ciardelli, R., Haumont, D. and Kirsch-Volders, M...
  11. Mahaffey D, Gorbea C, Rechsteiner M. Evidence that DNA replication is not regulated by ubiquitin-dependent proteolysis in Xenopus egg extract. Exp Cell Res. 2003;288:225-34 pubmed
    ..However, mitotic progression was halted, showing that the inhibitors were functional. We conclude that initiation of DNA replication is not regulated by Ub-dependent proteolysis in the early Xenopus cell cycle. ..
  12. POXLEITNER M, Dawson S, Cande W. Cell cycle synchrony in Giardia intestinalis cultures achieved by using nocodazole and aphidicolin. Eukaryot Cell. 2008;7:569-74 pubmed publisher
    ..The research presented here demonstrates reversible cell cycle arrest in G(1)/S and G(2)/M with aphidicolin and nocodazole, respectively...
  13. Collins N, Poot R, Kukimoto I, García Jiménez C, Dellaire G, Varga Weisz P. An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nat Genet. 2002;32:627-32 pubmed
    ..Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin. ..
  14. Howlett N, Taniguchi T, Durkin S, D Andrea A, Glover T. The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability. Hum Mol Genet. 2005;14:693-701 pubmed
    ..Here, we have characterized the role of the FA pathway in response to DNA replicative stress by aphidicolin (APH) and hydroxyurea (HU). The FA pathway is strongly activated in response to both agents...
  15. Shimura T, Martin M, Torres M, Gu C, Pluth J, DeBernardi M, et al. DNA-PK is involved in repairing a transient surge of DNA breaks induced by deceleration of DNA replication. J Mol Biol. 2007;367:665-80 pubmed
    ..These observations suggest that DNA-PK is involved in setting a high threshold for the ATR-Chk1-mediated S-phase checkpoint by promptly repairing DNA breaks that appear immediately following inhibition of DNA replication. ..
  16. Groschel B, Bushman F. Cell cycle arrest in G2/M promotes early steps of infection by human immunodeficiency virus. J Virol. 2005;79:5695-704 pubmed
    ..of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases...
  17. Waga S, Masuda T, Takisawa H, Sugino A. DNA polymerase epsilon is required for coordinated and efficient chromosomal DNA replication in Xenopus egg extracts. Proc Natl Acad Sci U S A. 2001;98:4978-83 pubmed
    ..These findings strongly suggest that Pol epsilon, along with Pol alpha and Pol delta, is necessary for coordinated chromosomal DNA replication in eukaryotic cells. ..
  18. Kayser O, Kiderlen A, Bertels S, Siems K. Antileishmanial activities of aphidicolin and its semisynthetic derivatives. Antimicrob Agents Chemother. 2001;45:288-92 pubmed
    b>Aphidicolin and a series of semisynthetic aphidicolan derivatives have been identified in in vitro tests as novel drugs with antiparasitic potential...
  19. Chang D, Lupardus P, Cimprich K. Monoubiquitination of proliferating cell nuclear antigen induced by stalled replication requires uncoupling of DNA polymerase and mini-chromosome maintenance helicase activities. J Biol Chem. 2006;281:32081-8 pubmed
    ..Using Xenopus egg extracts, we show that ultraviolet radiation and aphidicolin treatment induce the mono- and diubiquitination of PCNA...
  20. Parlanti E, Fortini P, MacPherson P, Laval J, Dogliotti E. Base excision repair of adenine/8-oxoguanine mispairs by an aphidicolin-sensitive DNA polymerase in human cell extracts. Oncogene. 2002;21:5204-12 pubmed
    ..Repair synthesis on either strand is completely inhibited by aphidicolin suggesting that a replicative DNA polymerase is involved in the gap filling...
  21. Tedeschi B, Cicchetti R, Argentin G, Caporossi D, Pittaluga M, Parisi P, et al. Aphidicolin and bleomycin induced chromosome damage as biomarker of mutagen sensitivity: a twin study. Mutat Res. 2004;546:55-64 pubmed
    The induction of chromosome damage in cultured human lymphocytes by in vitro treatments with aphidicolin (APC) and bleomycin (BLM) has been proposed as test of sensitivity to mutagens...
  22. Zachos G, Rainey M, Gillespie D. Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects. EMBO J. 2003;22:713-23 pubmed
    ..Furthermore, Chk1-dependent processes promote tumour cell survival after perturbations of DNA structure or metabolism. ..
  23. Arlt M, Ozdemir A, Birkeland S, Lyons R, Glover T, Wilson T. Comparison of constitutional and replication stress-induced genome structural variation by SNP array and mate-pair sequencing. Genetics. 2011;187:675-83 pubmed publisher
    ..SNP) arrays and mate-pair sequencing-to compare CNVs that occur constitutionally to those that arise following aphidicolin-induced DNA replication stress in the same human cells...
  24. Casper A, Nghiem P, Arlt M, Glover T. ATR regulates fragile site stability. Cell. 2002;111:779-89 pubmed
    ..These findings have important implications for understanding both the mechanism of fragile site instability and the consequences of stalled replication in mammalian cells...
  25. Musio A, Montagna C, Mariani T, Tilenni M, Focarelli M, Brait L, et al. SMC1 involvement in fragile site expression. Hum Mol Genet. 2005;14:525-33 pubmed
    ..specific for gamma-H2AX, we show that very rare discrete nuclear foci appear 1 and 2 h after exposure to aphidicolin and/or RNAi-SMC1, but became more numerous and distinct after longer treatment times...
  26. Denison S, Simper R, Greenbaum I. How common are common fragile sites in humans: interindividual variation in the distribution of aphidicolin-induced fragile sites. Cytogenet Genome Res. 2003;101:8-16 pubmed
    To obtain an estimate of the variation in common fragile sites (CFSs) among individuals, aphidicolin (APC)-induced chromosomal breakage data were analyzed for 20 karyotypically normal adult humans...
  27. 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
    ..In the father of a patient with Beckwith-Wiedemann syndrome and a pure truncation of 18q22-qter, a new aphidicolin-sensitive fragile site on chromosome 18q22.2 (FRA18C) is described...
  28. Sfeir A, Kosiyatrakul S, Hockemeyer D, MacRae S, Karlseder J, Schildkraut C, et al. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell. 2009;138:90-103 pubmed publisher
    ..challenge to the DNA replication machinery, giving rise to replication-dependent defects that resemble those of aphidicolin-induced common fragile sites...
  29. Le Beau M, Rassool F, Neilly M, Espinosa R, Glover T, Smith D, et al. Replication of a common fragile site, FRA3B, occurs late in S phase and is delayed further upon induction: implications for the mechanism of fragile site induction. Hum Mol Genet. 1998;7:755-61 pubmed
    ..2 is the most highly expressed of the common fragile sites observed when DNA replication is perturbed by aphidicolin or folate stress. The molecular basis for chromosome fragility at FRA3B is unknown...
  30. Byun T, Pacek M, Yee M, Walter J, Cimprich K. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev. 2005;19:1040-52 pubmed
    ..cause the functional uncoupling of MCM helicase and DNA polymerase activities, an event previously shown for aphidicolin. Inhibition of uncoupling during elongation with inhibitors of MCM7 or Cdc45, a putative helicase cofactor, ..
  31. Rozier L, El Achkar E, Apiou F, Debatisse M. Characterization of a conserved aphidicolin-sensitive common fragile site at human 4q22 and mouse 6C1: possible association with an inherited disease and cancer. Oncogene. 2004;23:6872-80 pubmed
    ..sites conserved at the molecular level, and reveal an unexpected link between an inherited disease and an aphidicolin-sensitive region...
  32. Chen H, Lawrence C, Bryan S, Moses R. Aphidicolin inhibits DNA polymerase II of Escherichia coli, an alpha-like DNA polymerase. Nucleic Acids Res. 1990;18:7185-6 pubmed
  33. Sutterlin C, Hsu P, Mallabiabarrena A, Malhotra V. Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells. Cell. 2002;109:359-69 pubmed
    ..Based on our findings, we suggest that the pericentriolar Golgi organization is a sensor for controlling entry into mitosis in mammalian cells. ..
  34. Oehlmann M, Score A, Blow J. The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation. J Cell Biol. 2004;165:181-90 pubmed
    ..These results show that Cdc6 plays multiple roles in ensuring precise chromosome duplication. ..
  35. Pirzio L, Pichierri P, Bignami M, Franchitto A. Werner syndrome helicase activity is essential in maintaining fragile site stability. J Cell Biol. 2008;180:305-14 pubmed publisher
    ..We demonstrate that in response to mild doses of aphidicolin, WRN is efficiently relocalized in nuclear foci in replicating cells and that WRN deficiency is associated with ..
  36. Zachos G, Rainey M, Gillespie D. Chk1-dependent S-M checkpoint delay in vertebrate cells is linked to maintenance of viable replication structures. Mol Cell Biol. 2005;25:563-74 pubmed
  37. Parlanti E, Pascucci B, Terrados G, Blanco L, Dogliotti E. Aphidicolin-resistant and -sensitive base excision repair in wild-type and DNA polymerase beta-defective mouse cells. DNA Repair (Amst). 2004;3:703-10 pubmed
    ..of a single abasic site by wild-type and Pol beta-defective mouse cell extracts was analysed in the presence of aphidicolin, a specific inhibitor of replicative Pols...
  38. Sun D, Urrabaz R, Buzello C, Nguyen M. Induction of DNA ligase I by 1-beta-D-arabinosylcytosine and aphidicolin in MiaPaCa human pancreatic cancer cells. Exp Cell Res. 2002;280:90-6 pubmed
    ..An increase in DNA ligase I was also observed in cells treated with aphidicolin, another inhibitor of DNA synthesis that inhibits DNA polymerases without incorporating itself into DNA, ..
  39. Marheineke K, Hyrien O. Aphidicolin triggers a block to replication origin firing in Xenopus egg extracts. J Biol Chem. 2001;276:17092-100 pubmed
    ..of origin firing, we have analyzed origin activation in sperm nuclei treated with the DNA polymerase inhibitor aphidicolin. Sperm chromatin was incubated in Xenopus egg extracts in the presence of aphidicolin and transferred to a ..
  40. Toledo F, Coquelle A, Svetlova E, Debatisse M. Enhanced flexibility and aphidicolin-induced DNA breaks near mammalian replication origins: implications for replicon mapping and chromosome fragility. Nucleic Acids Res. 2000;28:4805-13 pubmed
    Common fragile sites are chromosomal loci prone to breakage and rearrangement that can be induced by aphidicolin, an inhibitor of DNA polymerases...
  41. Ge X, Jackson D, Blow J. Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress. Genes Dev. 2007;21:3331-41 pubmed
    ..We propose that checkpoint kinase activity can preferentially suppress initiation within inactive replicon clusters, thereby directing new initiation events toward active clusters that are experiencing replication problems. ..
  42. Arlt M, Casper A, Glover T. Common fragile sites. Cytogenet Genome Res. 2003;100:92-100 pubmed
    b>Aphidicolin-induced common fragile sites are site-specific gaps or breaks seen on metaphase chromosomes after partial inhibition of DNA synthesis...
  43. Tsao C, Geisen C, Abraham R. Interaction between human MCM7 and Rad17 proteins is required for replication checkpoint signaling. EMBO J. 2004;23:4660-9 pubmed
    ..cells, depletion of either hRad17 or hMCM7 with small-interfering RNA suppressed ultraviolet (UV) light- or aphidicolin-induced hChk1 phosphorylation, and abolished UV-induced S-phase checkpoint activation...
  44. Woodward A, Gohler T, Luciani M, Oehlmann M, Ge X, Gartner A, et al. Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006;173:673-83 pubmed
  45. Mrasek K, Schoder C, Teichmann A, Behr K, Franze B, Wilhelm K, et al. Global screening and extended nomenclature for 230 aphidicolin-inducible fragile sites, including 61 yet unreported ones. Int J Oncol. 2010;36:929-40 pubmed
    ..According to information available from human genome browsers aphidicolin, an inhibitor of DNA replication induces 77 of 88 known common FS...
  46. Nicodemo D, Coppola G, Pauciullo A, Cosenza G, Ramunno L, Ciotola F, et al. Chromosomal expression and localization of aphidicolin-induced fragile sites in the standard karyotype of river buffalo (Bubalus bubalis). Cytogenet Genome Res. 2008;120:178-82 pubmed publisher
    The present study reports on the chromosomal expression and localization of aphidicolin-induced fragile sites in the standard karyotype of river buffalo (Bubalus bubalis, 2n = 50) with the aim of establishing a 'fragile site map' of the ..
  47. Quelo A, Verbelen J. Bromodeoxyuridine DNA fiber technology in plants: replication origins and DNA synthesis in tobacco BY-2 cells under prolonged treatment with aphidicolin. Protoplasma. 2004;223:197-202 pubmed
    ..Furthermore, the data confirm our previous observation that DNA synthesis is not totally blocked by aphidicolin. Bromodeoxyuridine incorporation into DNA was obvious from 24 h onwards after treatment with aphidicolin.
  48. Wan C, Kulkarni A, Wang Y. ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment. Mutat Res. 2010;686:39-46 pubmed publisher
    ..Interestingly, the amount of ATR protein that bound to three regions of FRA3B peaked at 0.4microM aphidicolin (APH) treatment and decreased again at higher concentrations of APH...
  49. Sawińska M, Schmitt J, Sagulenko E, Westermann F, Schwab M, Savelyeva L. Novel aphidicolin-inducible common fragile site FRA9G maps to 9p22.2, within the C9orf39 gene. Genes Chromosomes Cancer. 2007;46:991-9 pubmed
    ..Here, we identified a novel aphidicolin-inducible common fragile site FRA9G, which maps to chromosomal band 9p22.2...
  50. Nethanel T, Reisfeld S, Dinter Gottlieb G, Kaufmann G. An Okazaki piece of simian virus 40 may be synthesized by ligation of shorter precursor chains. J Virol. 1988;62:2867-73 pubmed
    It is generally accepted that an aphidicolin-sensitive DNA polymerase elongates the eucaryotic RNA primer (iRNA) into a mature Okazaki piece reaching ca. 200 nucleotides...
  51. Rassool F, Le Beau M, Shen M, Neilly M, Espinosa R, Ong S, et al. Direct cloning of DNA sequences from the common fragile site region at chromosome band 3p14.2. Genomics. 1996;35:109-17 pubmed
    ..The results imply that breakage occurs at variable positions within a large region (at least on the order of 85 kb). Together, these data suggest that the structure of FRA3B differs from that of rare fragile sites...
  52. Hubeek I, Peters G, Broekhuizen A, Sargent J, Gibson B, Creutzig U, et al. Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia. Br J Haematol. 2005;131:219-22 pubmed
    ..Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic...
  53. Kayser O. Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against leishmania infected macrophages. Int J Pharm. 2000;196:253-6 pubmed
    ..Of these compounds, aphidicolin, a tetradecanhydro-3,9-dihydroxy-4,11b-dimethyl-8, 11a-methano-11aH-cyclo-hepta[a]naphthalin-4,9-dimethanol+ ++ ..
  54. Wang H, Hays J. Mismatch repair in human nuclear extracts. Time courses and ATP requirements for kinetically distinguishable steps leading to tightly controlled 5' to 3' and aphidicolin-sensitive 3' to 5' mispair-provoked excision. J Biol Chem. 2002;277:26143-8 pubmed
    ..In both substrates, corrected products appeared at fractional rates of 0.0027 of final yield per second. Aphidicolin, known to inhibit both the DNA synthesis and 3' to 5' exonuclease activities of polymerases delta and epsilon, ..
  55. Görisch S, Sporbert A, Stear J, Grunewald I, Nowak D, Warbrick E, et al. Uncoupling the replication machinery: replication fork progression in the absence of processive DNA synthesis. Cell Cycle. 2008;7:1983-90 pubmed
    ..and their response to polymerase stalling by inhibition of the DNA polymerases in living mammalian cells with aphidicolin. We observed little change in the behaviour of proteins involved in the initiation of DNA replication...
  56. Marheineke K, Hyrien O. Control of replication origin density and firing time in Xenopus egg extracts: role of a caffeine-sensitive, ATR-dependent checkpoint. J Biol Chem. 2004;279:28071-81 pubmed
    ..We also show that caffeine allows more early origin firing with low levels of aphidicolin treatment but not higher levels...
  57. Speit G, Schütz P, Hoffmann H. Enhancement of genotoxic effects in the comet assay with human blood samples by aphidicolin. Toxicol Lett. 2004;153:303-10 pubmed
    ..of such an approach we performed an experimental study with human blood and tested the enhancing effect of aphidicolin (APC) on DNA effects induced by different mutagens...
  58. Ruiz Herrera A, Garcia F, Frönicke L, Ponsà M, Egozcue J, Caldés M, et al. Conservation of aphidicolin-induced fragile sites in Papionini (Primates) species and humans. Chromosome Res. 2004;12:683-90 pubmed
    ..We delineated the interspecific homology of chromosome bands expressing aphidicolin-induced fragile sites of homologues to human chromosomes 1, 3, 5, 7, 18 and X by the comparative FISH of human ..
  59. El Achkar E, Gerbault Seureau M, Muleris M, Dutrillaux B, Debatisse M. Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites. Proc Natl Acad Sci U S A. 2005;102:18069-74 pubmed
    ..Most of these sites are induced after perturbation of the replication dynamics, notably by aphidicolin treatment...
  60. Yoo H, Kumagai A, Shevchenko A, Shevchenko A, Dunphy W. Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase. Cell. 2004;117:575-88 pubmed
    ..protein Claspin is essential for the ATR-dependent activation of Chk1 in Xenopus egg extracts containing aphidicolin-induced DNA replication blocks...
  61. Rodriguez V, Llambí S, Postiglioni A, Guevara K, Rincon G, Fernandez G, et al. Localisation of aphidicolin-induced break points in Holstein-Friesian cattle (Bos taurus) using RBG-banding. Genet Sel Evol. 2002;34:649-56 pubmed
    ..The majority of common fragile sites are induced by aphidicolin. Aphidicolin was used at two different concentrations (0.15 and 0...
  62. Lee K, Kim H, Sung J, Park K, Kim M. Defective neurite outgrowth in aphidicolin/cAMP-induced motor neurons expressing mutant Cu/Zn superoxide dismutase. Int J Dev Neurosci. 2002;20:521-6 pubmed
    ..Cells were differentiated by dibutyryl cAMP and aphidicolin. The mutant showed a defect in neurite outgrowth and had decreased viability...
  63. Marusyk A, Wheeler L, Mathews C, DeGregori J. p53 mediates senescence-like arrest induced by chronic replicational stress. Mol Cell Biol. 2007;27:5336-51 pubmed
    ..Chronic exposure to low concentrations of hydroxyurea, aphidicolin, or etoposide induced irreversible cell cycle arrest after several population doublings...
  64. Feijoo C, Hall Jackson C, Wu R, Jenkins D, Leitch J, Gilbert D, et al. Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol. 2001;154:913-23 pubmed
    ..Thus, Chk1 is apparently necessary for an intra-S phase checkpoint, ensuring that activation of late replication origins is blocked and arrested replication fork integrity is maintained when DNA synthesis is inhibited. ..
  65. Michael W, Ott R, Fanning E, Newport J. Activation of the DNA replication checkpoint through RNA synthesis by primase. Science. 2000;289:2133-7 pubmed
    ..These findings identify the RNA portion of the primer as an important component of the signal that activates the replication checkpoint. ..
  66. Luciani M, Oehlmann M, Blow J. Characterization of a novel ATR-dependent, Chk1-independent, intra-S-phase checkpoint that suppresses initiation of replication in Xenopus. J Cell Sci. 2004;117:6019-30 pubmed
    ..We also show that low concentrations of the DNA-polymerase inhibitor aphidicolin, which only slightly slows replication-fork progression, strongly suppress further initiation events...