Tumor suppressor Ing1b facilitates DNA repair and prevents oxidative stress induced cell death.
Inhibitor of growth (ING) family of proteins are known to coordinate with histone acetyltransferases and regulate the key events of cell cycle and DNA repair. Previous work from our lab showed that Ing1b regulated the nucleotide excision repair by facilitating histone acetylation and subsequent chromatin relaxation. Further, it was also shown that Ing1b protected the cells from genomic instability induced cell death by promoting ubiquitination of proliferating cell nuclear antigen (PCNA). In the present study we explored the role of Ing1b in the repair of oxidized DNA and prevention of oxidative stress induced genotoxic cell death. Using HCT116 cells we show that Ing1b protein expression is induced by treatment with H2O2. Ing1b lacking cells showed decreased ability to repair the oxidized DNA. PCNA monoubiquitination, a critical event of DNA repair was blunted in Ing1b knock down cells and augmented in Ing1b over expressing cells. Moreover, oxidative stress induced cell death was higher in cells lacking Ing1b whereas it was lower in Ing1b over expressing cells. Finally we show that inhibition of histone deacetylases, rescued the Ing1b knock down cells from cytotoxic effects of H2O2 treatment.
Department of Dermatology and Skin Science, University of British Columbia, Research Pavilion, 828 West, 10th Avenue, Vancouver, BC, V5Z 1L8, Canada, anand.rotte@ubc.ca.
Anand
A
Rotte
Gang
G
Li
Madhuri
M
Bhandaru
D016923:Cell Death; D004249:DNA Damage; D004260:DNA Repair; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D056572:Histone Deacetylase Inhibitors; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; D006861:Hydrogen Peroxide