SV40 T antigen interacts with Nbs1 to disrupt DNA replication control

Xiaohua Wu, Dror Avni, Takuya Chiba, Feng Yan, Qiping Zhao, Yafang Lin, Henry Heng, David Livingston

Research output: Contribution to journalArticle

69 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1305-1316
Number of pages12
JournalGenes and Development
Volume18
Issue number11
DOIs
Publication statusPublished - 2004 Jun 1
Externally publishedYes

Fingerprint

Nijmegen Breakage Syndrome
Simian virus 40
Viral Tumor Antigens
DNA Replication
Chromosomal Instability
Replicon
DNA Viruses
Tetraploidy
Oncogene Proteins
DNA
Viral DNA
Hypersensitivity
Fibroblasts
Genome
Radiation

Keywords

  • DNA replication
  • Endoreduplication
  • Mammalian cells
  • Nbs1
  • SV40 origin
  • SV40 T

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Wu, X., Avni, D., Chiba, T., Yan, F., Zhao, Q., Lin, Y., ... Livingston, D. (2004). SV40 T antigen interacts with Nbs1 to disrupt DNA replication control. Genes and Development, 18(11), 1305-1316. https://doi.org/10.1101/gad.1182804

SV40 T antigen interacts with Nbs1 to disrupt DNA replication control. / Wu, Xiaohua; Avni, Dror; Chiba, Takuya; Yan, Feng; Zhao, Qiping; Lin, Yafang; Heng, Henry; Livingston, David.

In: Genes and Development, Vol. 18, No. 11, 01.06.2004, p. 1305-1316.

Research output: Contribution to journalArticle

Wu, X, Avni, D, Chiba, T, Yan, F, Zhao, Q, Lin, Y, Heng, H & Livingston, D 2004, 'SV40 T antigen interacts with Nbs1 to disrupt DNA replication control', Genes and Development, vol. 18, no. 11, pp. 1305-1316. https://doi.org/10.1101/gad.1182804
Wu, Xiaohua ; Avni, Dror ; Chiba, Takuya ; Yan, Feng ; Zhao, Qiping ; Lin, Yafang ; Heng, Henry ; Livingston, David. / SV40 T antigen interacts with Nbs1 to disrupt DNA replication control. In: Genes and Development. 2004 ; Vol. 18, No. 11. pp. 1305-1316.
@article{28267292a350422d9ece6f01d7ec3890,
title = "SV40 T antigen interacts with Nbs1 to disrupt DNA replication control",
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.",
keywords = "DNA replication, Endoreduplication, Mammalian cells, Nbs1, SV40 origin, SV40 T",
author = "Xiaohua Wu and Dror Avni and Takuya Chiba and Feng Yan and Qiping Zhao and Yafang Lin and Henry Heng and David Livingston",
year = "2004",
month = "6",
day = "1",
doi = "10.1101/gad.1182804",
language = "English",
volume = "18",
pages = "1305--1316",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "11",

}

TY - JOUR

T1 - SV40 T antigen interacts with Nbs1 to disrupt DNA replication control

AU - Wu, Xiaohua

AU - Avni, Dror

AU - Chiba, Takuya

AU - Yan, Feng

AU - Zhao, Qiping

AU - Lin, Yafang

AU - Heng, Henry

AU - Livingston, David

PY - 2004/6/1

Y1 - 2004/6/1

N2 - 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.

AB - 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.

KW - DNA replication

KW - Endoreduplication

KW - Mammalian cells

KW - Nbs1

KW - SV40 origin

KW - SV40 T

UR - http://www.scopus.com/inward/record.url?scp=2642527155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642527155&partnerID=8YFLogxK

U2 - 10.1101/gad.1182804

DO - 10.1101/gad.1182804

M3 - Article

C2 - 15175262

AN - SCOPUS:2642527155

VL - 18

SP - 1305

EP - 1316

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 11

ER -