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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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
Issue number11
StatePublished - 1 Jun 2004
Externally publishedYes


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


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