SV40 T antigen interacts with Nbs1 to disrupt DNA replication control

Wu, Xiaohua; Avni, Dror; Chiba, Takuya; Feng, Yongzeng; Zhao, Qiuyan; Lin, Yuan; Heng, Henry H.Q.; Livingston, David M.

doi:10.1101/gad.1182804

Cited by 78 publications

(75 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, loss of Nbs1 allows cells to undergo more than a single round of DNA replication per cell cycle. Consistent with this finding, immortalized human NBS fibroblasts display endoreduplication and tetraploidy when a dominant interfering N-terminal Nbs1 fragment is ectopically expressed in these cells in vitro (34). We conclude that physiological levels of Nbs1 are required to maintain the integrity of chromosome structure as well as chromosome number.…”

Section: Intra-s-phase Checkpoint and Proliferation Defects In Nbs1supporting

confidence: 69%

Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking Nbs1

Reina‐San‐Martin

Nussenzweig

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

129

View full text Add to dashboard Cite

Mre11, Rad50, and Nbs1 form an evolutionarily conserved protein complex (Mre11-Rad50 -Nbs1, MRN) that has been proposed to function as a DNA damage sensor. Hypomorphic mutations in Mre11 and Nbs1 result in the human ataxia-telangiectasia-like disorder and Nijmegen breakage syndrome (NBS), respectively. In contrast, complete inactivation of Mre11, Rad50, or Nbs1 leads to early embryonic lethality, suggesting that the hypomorphic mutations may fail to reveal some of the essential functions of MRN. Here, we use Cre-loxP-mediated recombination to restrict Nbs1 deletion to B lymphocytes. We find that disruption of Nbs1 results in the accumulation of high levels of spontaneous DNA damage, impaired proliferation, and chromosomal endoreduplication. Moreover, we show that Ig class-switch recombination (CSR) is diminished in Nbs1-deficient B cells. The CSR defect is B cellintrinsic, independent of switch-region transcription, and a consequence of inefficient recombination at the DNA level. Our findings reveal that Nbs1 is critical for efficient Ig CSR and maintenance of the integrity of chromosomal structure and number.

show abstract

Section: Intra-s-phase Checkpoint and Proliferation Defects In Nbs1supporting

confidence: 69%

Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking Nbs1

Reina‐San‐Martin

Nussenzweig

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

129

View full text Add to dashboard Cite

show abstract

“…Their findings show that the MRN complex acts upstream of ATM during adenovirus infection and that the combined actions of the MRN complex and ATM in DNA repair and checkpoint control block virus replication and infection. In support of this, Wu et al (2004) also showed that SV40 large T antigen can interact with Nbs1 and that this interaction disrupts Nbs1-mediated suppression of SV40 replication. Recently, infection of cells with herpes simplex virus (HSV) was also shown to induce an ATM-and MRN-dependent DNA-damage response, including ATM autophosphorylation and phosphorylation of ATM target substrates.…”

Section: The Role Of the Mrn Complex In Atm Activationmentioning

confidence: 67%

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

2007

View full text Add to dashboard Cite

The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and specifically activated in response to DNA double-strand breaks in eukaryotic cells. In this review, we summarize recent insights into the mechanism of ATM activation, focusing on the role of the Mre11/Rad50/Nbs1 (MRN) complex in this process. We also compare observations of the ATM activation process in different biological systems and highlight potential candidates for cellular factors that may participate in regulating ATM activity in human cells.

show abstract

“…Polyclonal antibodies against Mre11 (D27) and Nbs1 (D29) were described previously (49,50). Other antibodies include anti-Rad50 and anti-Myc-9E10 (Novus Biologicals), anti-Ku70 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA), anti-FLAG-M2 (Sigma), anti-HA and anti-MDC1 (Sigma), anti-H2AX (Bethyl), and anti-GST and anti-RPA2 (Oncogene).…”

Section: Methodsmentioning

confidence: 99%

The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination

Truong

Aslanian

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background:The Mre11-Rad50-Nbs1 (MRN) complex and the ubiquitin E3 ligase RNF8 play important roles in DNA DSB repair. Results: RNF8 interacts with and ubiquitinates Nbs1 to promote binding of Nbs1 to DSBs and HR-mediated DSB repair. Conclusion: Nbs1 ubiquitination by RNF8 is important for Nbs1 recruitment to DSBs and HR-mediated repair of DSBs. Significance: These studies help to understand how ubiquitination modifications contribute to DSB repair and genome stability maintenance in mammalian cells.

show abstract

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.

Cited by 78 publications

References 63 publications

Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking Nbs1

Genomic instability, endoreduplication, and diminished Ig class-switch recombination in B cells lacking Nbs1

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

The RING Finger Protein RNF8 Ubiquitinates Nbs1 to Promote DNA Double-strand Break Repair by Homologous Recombination

Contact Info

Product

Resources

About