4 230

Cited 12 times in

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

Authors
 JONG HWA LEE  ;  KYUNG HWAN KIM  ;  TOMOHIRO MORIO  ;  HYEYOUNG KIM 
Citation
 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, Vol.1091 : 76-82, 2006 
Journal Title
 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 
ISSN
 0077-8923 
Issue Date
2006
MeSH
Ataxia Telangiectasia/genetics* ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/physiology* ; Cell Death/drug effects ; Cell Death/physiology ; Cell Line ; DNA Damage ; DNA Helicases/metabolism* ; DNA Repair/drug effects ; DNA Repair/physiology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/physiology* ; Enzyme Activation/physiology ; Fibroblasts/drug effects ; Fibroblasts/enzymology* ; Humans ; Hydrogen Peroxide/pharmacology* ; Ku Autoantigen ; Oxidants/physiology ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/physiology* ; Transfection ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/physiology*
Keywords
ataxia‐telangiectasia‐mutated ; oxidative stress ; A‐T fibroblasts ; Ku
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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1196/annals.1378.056/abstract
DOI
10.1196/annals.1378.056
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/110778
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse