Ataxia-telangiectasia-mutated-dependent activation of Ku in human fibroblasts exposed to hydrogen peroxide

Hwa Lee Jong, Hwan Kim Kyung, Tomohiro Morio, Hyeyoung Kim

Research output: Chapter in Book/Report/Conference proceedingConference contribution

12 Citations (Scopus)

Abstract

DNA is damaged in cells during cell replication, by infection, or by various environmental stresses. The damaged cells stop cell cycle, repair damaged DNA, and when repaired progress into the next cell cycle stage. But when the attempt to repair the damage fails, the cells undergo apoptosis. The most deleterious damage of all is double-strand DNA breaks (DSBs), where ATM (ataxia-telangiectasia-mutated) serves as a sensor. The ATM pathway culminates in DNA repair through nonhomologous end-joining or through homologous recombination. Upon DNA damage, the DNA repair protein Ku70/80 translocates into the nucleus, which may be mediated by ATM. Previously, we found that pancreatic acinar cells undergo apoptosis upon oxidative stress, and the cell death stems from nuclear loss of Ku70/80. This study aims to investigate whether ATM has a role in Ku activation and prevention of cell death induced by oxidative stress (hydrogen peroxide) using A-T fibroblasts stably transfected with human full-length ATM cDNA or empty vector. As a result, hydrogen peroxide-induced cell death was augmented in A-T cells transfected with empty vector while cell death was prevented in A-T fibroblasts stably transfected with human full-length ATM cDNA. Ku DNA-binding activity induced by hydrogen peroxide treatment was increased in the A-T fibroblasts stably transfected with human full-length ATM cDNA compared to that in A-T cells transfected with empty vector. The results suggest that ATM may be essential for Ku activation to repair DNA damage from oxidative stress and prevent cell death caused by oxidative stress.

Original languageEnglish
Title of host publicationSignal Transduction Pathways, Part B
Subtitle of host publicationStress Signalling and Transcriptional Control
PublisherBlackwell Publishing Inc.
Pages76-82
Number of pages7
ISBN (Print)1573316474, 9781573316477
DOIs
Publication statusPublished - 2006 Dec

Publication series

NameAnnals of the New York Academy of Sciences
Volume1091
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Jong, H. L., Kyung, H. K., Morio, T., & Kim, H. (2006). Ataxia-telangiectasia-mutated-dependent activation of Ku in human fibroblasts exposed to hydrogen peroxide. In Signal Transduction Pathways, Part B: Stress Signalling and Transcriptional Control (pp. 76-82). (Annals of the New York Academy of Sciences; Vol. 1091). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1378.056