Functional links between transcription, DNA repair and apoptosis.
DNA damage initiates damage response pathways, cell cycle arrest and apoptosis. These processes act in a concerted fashion and remain functionally linked through mechanisms not completely understood. Programmed cell death, referred to as apoptosis, is a tightly regulated phenomenon ensuring that cells that accumulate irreversible DNA damage do not replicate. Interestingly, hyperacetylation of histone proteins, which alters transcription patterns and appears linked to DNA repair, also induces apoptosis, suggesting that aspects of chromatin modification link these very distinct processes. Modulating chromatin structure in the absence of any DNA lesions also activates key DNA damage-signalling proteins, further supporting the role of higher-order chromatin structure in mediating stress responses. This review will present an overview of the epigenetic control of eukaryotic genomes by chromatin remodelling as it pertains to DNA damage and highlight the potential role of the ING PHD proteins in linking apoptosis and DNA repair to gene transcription.
Berardi
P
P
Department of Biochemistry and Molecular Biology and Oncology, Southern Alberta Cancer Research Centre, University of Calgary, 3330 Hospital Drive N.W., Heritage Medical Research Building, T2N 4N1, Calgary, Alberta, Canada.
Russell
M
M
El-Osta
A
A
Riabowol
K
K
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D016922:Cellular Senescence; D002843:Chromatin / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins / Q000502:physiology; D012313:RNA / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D012313:RNA