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PMID: 15175262 Published · ppublish English Journal Article

SV40 T antigen interacts with Nbs1 to disrupt DNA replication control.

Genes & development ·Vol. 18 ·No. 11 ·2004-06-01 ·Pages 1305-16

Wu X, Avni D, Chiba T, Yan F, Zhao Q, Lin Y, Heng H, Livingston D

Abstract

Nijmegen breakage syndrome (NBS) is characterized by radiation hypersensitivity, chromosomal instability, and predisposition to cancer. Nbs1, the NBS protein, forms a tight complex with Mre11 and Rad50, and these interactions contribute to proper double-strand break repair. The simian virus 40 (SV40) oncoprotein, large T antigen (T), also interacts with Nbs1, and T-containing cells experience chromosomal hyperreplication in a manner dependent on T/Nbs1 complex formation. A substantial fraction of NBS-deficient fibroblasts reinitiate DNA replication in discrete regions, and wild-type Nbs1 corrects this defect. Similarly, synthesis of an N-terminal Nbs1 fragment induced DNA rereplication and tetraploidy, in NBS-deficient but not NBS-proficient cells. Moreover, SV40 origin-containing DNA hyperreplicated in T-containing NBS-deficient cells by comparison with T-containing, Nbs1-reconstituted derivatives. Thus, Nbs1 suppresses rereplication of cellular DNA and SV40 origin-containing replicons, and T targets Nbs1, thereby enhancing the yield of new SV40 genomes during viral DNA replication.

MeSH Terms
Acid Anhydride Hydrolases Antigens, Polyomavirus Transforming/genetics,metabolism Binding Sites Cell Cycle Proteins/genetics,metabolism,radiation effects Cells, Cultured DNA Damage/physiology DNA Repair Enzymes/genetics,metabolism DNA Replication/physiology DNA-Binding Proteins/genetics,metabolism Fibroblasts/physiology Humans MRE11 Homologue Protein Mutation Nuclear Proteins/genetics,metabolism,radiation effects Phosphorylation Radiation, Ionizing Replication Origin Virus Replication/genetics
Chemicals
Antigens, Polyomavirus Transforming Cell Cycle Proteins DNA-Binding Proteins MRE11 protein, human NBN protein, human Nuclear Proteins MRE11 Homologue Protein Acid Anhydride Hydrolases Rad50 protein, human DNA Repair Enzymes
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wu Xiaohua
Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA. xiaohwu@scripps.edu
Avni Dror
Chiba Takuya
Yan Feng
Zhao Qiping
Lin Yafang
Heng Henry
Livingston David
References (61)
61 references, click to expand
  1. Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells.
    EMBO J. 1999 Dec 1;18(23):6619-29 PMID: 10581236
  2. Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae.
    Genetics. 1995 Apr;139(4):1521-32 PMID: 7789757
  3. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.
    Nature. 2000 Apr 6;404(6778):613-7 PMID: 10766245
  4. ATM-dependent phosphorylation of nibrin in response to radiation exposure.
    Nat Genet. 2000 May;25(1):115-9 PMID: 10802669
  5. Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products.
    Nature. 2000 May 25;405(6785):473-7 PMID: 10839544
  6. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response.
    Nature. 2000 May 25;405(6785):477-82 PMID: 10839545
  7. RuvABC-dependent double-strand breaks in dnaBts mutants require recA.
    Mol Microbiol. 2000 Nov;38(3):565-74 PMID: 11069680
  8. DNA damage-dependent nuclear dynamics of the Mre11 complex.
    Mol Cell Biol. 2001 Jan;21(1):281-8 PMID: 11113202
  9. Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism.
    Cell. 1997 Jul 11;90(1):87-96 PMID: 9230305
  10. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization.
    Cell. 1997 Aug 22;90(4):785-95 PMID: 9288757
  11. hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.
    Mol Cell Biol. 1997 Oct;17(10):6087-96 PMID: 9315668
  12. Analysis of DNA replication by fluorescence in situ hybridization.
    Methods. 1997 Nov;13(3):259-70 PMID: 9441852
  13. A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage.
    Cell. 1995 Sep 8;82(5):841-7 PMID: 7671311
  14. Participation of the human beta-globin locus control region in initiation of DNA replication.
    Science. 1995 Nov 3;270(5237):815-9 PMID: 7481774
  15. Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae.
    Mol Cell Biol. 1996 May;16(5):2164-73 PMID: 8628283
  16. Once and only once upon a time: specifying and regulating origins of DNA replication in eukaryotic cells.
    Genes Dev. 1996 Nov 15;10(22):2819-30 PMID: 8918884
  17. Association of BRCA1 with Rad51 in mitotic and meiotic cells.
    Cell. 1997 Jan 24;88(2):265-75 PMID: 9008167
  18. DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication.
    Genes Dev. 1997 May 1;11(9):1098-110 PMID: 9159391
  19. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells.
    Nucleic Acids Res. 1997 Aug 1;25(15):2985-91 PMID: 9224597
  20. Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart.
    Annu Rev Genet. 1997;31:635-62 PMID: 9442910
  21. Activities of SV40 T antigen necessary for the induction of tetraploid DNA content in permissive CV-1 cells.
    Cytometry. 1998 Apr 1;31(4):251-9 PMID: 9551600
  22. In situ visualization of DNA double-strand break repair in human fibroblasts.
    Science. 1998 Apr 24;280(5363):590-2 PMID: 9554850
  23. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.
    Cell. 1998 May 1;93(3):467-76 PMID: 9590180
  24. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.
    Cell. 1998 May 1;93(3):477-86 PMID: 9590181
  25. DNA repair: the Nijmegen breakage syndrome protein.
    Curr Biol. 1998 Aug 27;8(17):R622-5 PMID: 9742394
  26. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.
    Mol Cell. 1998 Sep;2(3):317-28 PMID: 9774970
  27. A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication.
    Nature. 1998 Oct 8;395(6702):615-8 PMID: 9783589
  28. Regulation of DNA-replication origins during cell-cycle progression.
    Nature. 1998 Oct 8;395(6702):618-21 PMID: 9783590
  29. Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation.
    Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7376-81 PMID: 10377422
  30. The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage.
    J Biol Chem. 1999 Jul 9;274(28):19513-6 PMID: 10391882
  31. Cellular transformation by SV40 large T antigen: interaction with host proteins.
    Semin Cancer Biol. 2001 Feb;11(1):15-23 PMID: 11243895
  32. Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice.
    Curr Biol. 2001 Jan 23;11(2):105-9 PMID: 11231126
  33. DNA replication: building the perfect switch.
    Curr Biol. 2001 May 1;11(9):R367-70 PMID: 11369250
  34. Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis.
    Mol Cell Biol. 2001 Sep;21(17):6006-16 PMID: 11486038
  35. Mre11 protein complex prevents double-strand break accumulation during chromosomal DNA replication.
    Mol Cell. 2001 Jul;8(1):137-47 PMID: 11511367
  36. Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage.
    Mol Cell. 2003 Sep;12(3):735-46 PMID: 14527418
  37. SV40 large T antigen promotes dephosphorylation of p130.
    J Biol Chem. 2003 Nov 21;278(47):46482-7 PMID: 12968030
  38. Induction of DNA synthesis by SV40.
    Proc Natl Acad Sci U S A. 1966 Aug;56(2):736-40 PMID: 4291013
  39. Simian virus 40 deoxyribonucleic acid synthesis: the viral replicon.
    J Virol. 1972 Oct;10(4):591-8 PMID: 4343541
  40. Viral DNA synthesis in cells infected by temperature-sensitive mutants of simian virus 40.
    J Virol. 1974 Jul;14(1):116-24 PMID: 4366021
  41. Studies on simian virus 40 excision from cellular chromosomes.
    Cold Spring Harb Symp Quant Biol. 1979;43 Pt 2:709-19 PMID: 226315
  42. Monoclonal antibodies specific for simian virus 40 tumor antigens.
    J Virol. 1981 Sep;39(3):861-9 PMID: 6169844
  43. In vitro mutagenesis of a putative DNA binding domain of SV40 large-T.
    Virology. 1984 Nov;139(1):109-37 PMID: 6093377
  44. A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection.
    Cell. 1989 May 19;57(4):659-66 PMID: 2541919
  45. Animal virus DNA replication.
    Annu Rev Biochem. 1989;58:671-717 PMID: 2549858
  46. Phosphorylation of large tumour antigen by cdc2 stimulates SV40 DNA replication.
    Nature. 1989 Oct 12;341(6242):503-7 PMID: 2552322
  47. Initiation of eukaryotic DNA replication in vitro.
    Annu Rev Cell Biol. 1989;5:197-245 PMID: 2557059
  48. A DNA replication-positive mutant of simian virus 40 that is defective for transformation and the production of infectious virions.
    J Virol. 1990 Jun;64(6):2912-21 PMID: 2159552
  49. The replication functions of SV40 T antigen are regulated by phosphorylation.
    Cell. 1990 Jun 1;61(5):735-8 PMID: 2160857
  50. Identification of simian virus 40 T-antigen residues important for specific and nonspecific binding to DNA and for helicase activity.
    J Virol. 1990 Oct;64(10):4858-65 PMID: 2168972
  51. The in vitro replication of DNA containing the SV40 origin.
    J Biol Chem. 1990 Oct 25;265(30):18043-6 PMID: 1976634
  52. Simian virus 40 large T-antigen function is required for induction of tetraploid DNA content during lytic infection.
    J Virol. 1992 Jul;66(7):4576-9 PMID: 1318419
  53. Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62 PMID: 1495986
  54. High-resolution mapping of mammalian genes by in situ hybridization to free chromatin.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9509-13 PMID: 1384055
  55. Association of p53 binding and immortalization of primary C57BL/6 mouse embryo fibroblasts by using simian virus 40 T-antigen mutants bearing internal overlapping deletion mutations.
    J Virol. 1993 Apr;67(4):1817-29 PMID: 8383212
  56. Modes of DAPI banding and simultaneous in situ hybridization.
    Chromosoma. 1993 May;102(5):325-32 PMID: 8325164
  57. The DNA-binding domain of simian virus 40 tumor antigen has multiple functions.
    J Virol. 1993 Dec;67(12):7608-11 PMID: 8230479
  58. Replication structure of the human beta-globin gene domain.
    Nature. 1993 Dec 9;366(6455):588-90 PMID: 8255298
  59. Induction of tetraploid DNA content by simian virus 40 is dependent on T-antigen function in the G2 phase of the cell cycle.
    J Virol. 1994 Jun;68(6):4028-30 PMID: 8189537
  60. A novel DNA replication origin identified in the human heat shock protein 70 gene promoter.
    Mol Cell Biol. 1994 Sep;14(9):6386-97 PMID: 8065368
  61. Start sites of bidirectional DNA synthesis at the human lamin B2 origin.
    Science. 2000 Mar 17;287(5460):2023-6 PMID: 10720330
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1182804
Email
xiaohwu@scripps.edu
Published
2004-06-01
Pages
1305-16
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC420356
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1182804 PMC Full Text View journal details
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