Skip to main content

Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response.

Publication ,  Journal Article
Chandhasin, C; Ducu, RI; Berkovich, E; Kastan, MB; Marriott, SJ
Published in: J Virol
July 2008

Genomic instability, a hallmark of leukemic cells, is associated with malfunctioning cellular responses to DNA damage caused by defective cell cycle checkpoints and/or DNA repair. Adult T-cell leukemia, which can result from infection with human T-cell leukemia virus type 1 (HTLV-1), is associated with extensive genomic instability that has been attributed to the viral oncoprotein Tax. How Tax influences cellular responses to DNA damage to mediate genomic instability, however, remains unclear. Therefore, we investigated the effect of Tax on cellular pathways involved in recognition and repair of DNA double-strand breaks. Premature attenuation of ATM kinase activity and reduced association of MDC1 with repair foci were observed in Tax-expressing cells. Following ionizing radiation-induced S-phase checkpoint activation, Tax-expressing cells progressed more rapidly than non-Tax-expressing cells toward DNA replication. These results demonstrate that Tax expression may allow premature DNA replication in the presence of genomic lesions. Attempts to replicate in the presence of these lesions would result in gradual accumulation of mutations, leading to genome instability and cellular transformation.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 2008

Volume

82

Issue

14

Start / End Page

6952 / 6961

Location

United States

Related Subject Headings

  • Virology
  • Tumor Suppressor Proteins
  • Trans-Activators
  • T-Lymphocytes
  • Protein Serine-Threonine Kinases
  • Nuclear Proteins
  • Humans
  • Human T-lymphotropic virus 1
  • Gene Products, tax
  • DNA-Binding Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chandhasin, C., Ducu, R. I., Berkovich, E., Kastan, M. B., & Marriott, S. J. (2008). Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response. J Virol, 82(14), 6952–6961. https://doi.org/10.1128/JVI.02331-07
Chandhasin, Chandtip, Razvan I. Ducu, Elijahu Berkovich, Michael B. Kastan, and Susan J. Marriott. “Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response.J Virol 82, no. 14 (July 2008): 6952–61. https://doi.org/10.1128/JVI.02331-07.
Chandhasin C, Ducu RI, Berkovich E, Kastan MB, Marriott SJ. Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response. J Virol. 2008 Jul;82(14):6952–61.
Chandhasin, Chandtip, et al. “Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response.J Virol, vol. 82, no. 14, July 2008, pp. 6952–61. Pubmed, doi:10.1128/JVI.02331-07.
Chandhasin C, Ducu RI, Berkovich E, Kastan MB, Marriott SJ. Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response. J Virol. 2008 Jul;82(14):6952–6961.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 2008

Volume

82

Issue

14

Start / End Page

6952 / 6961

Location

United States

Related Subject Headings

  • Virology
  • Tumor Suppressor Proteins
  • Trans-Activators
  • T-Lymphocytes
  • Protein Serine-Threonine Kinases
  • Nuclear Proteins
  • Humans
  • Human T-lymphotropic virus 1
  • Gene Products, tax
  • DNA-Binding Proteins