SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements(699 views) Antoniali G, Lirussi L, D'Ambrosio C, Dal Piaz F, Vascotto C, Casarano E, Marasco D, Scaloni A, Fogolari F, Tell G
Mol Biol Cell (ISSN: 1059-1524), 2014 Feb 15; 25(4): 532-547.
Keywords: Apex1 Protein, Human, Cell Nucleus Antigen, Dna (apurinic Or Apyrimidinic Site) Lyase, Dna Binding Protein, Dna Glycosyltransferase, Hydrogen Peroxide, Ku Antigen, Mesylic Acid Methyl Ester, Oxoguanine Glycosylase 1, Protein Binding, Rna Polymerase Ii, Sirt1 Protein, Sirtuin 1, Small Interfering Rna, Antagonists And Inhibitors, Binding Site, Biology, Dna Damage, Dna Responsive Element, Drug Effects, Gene Expression Regulation, Genetic Transcription, Hela Cell Line, Human Genome, Metabolism, Molecular Genetics, Nucleotide Sequence, Signal Transduction, Base Sequence, Computational Biology, Dna Glycosylases, Dna-(apurinic Or Apyrimidinic Site) Lyase, Dna-Binding Proteins, Methyl Methanesulfonate, Molecular Sequence Annotation, Molecular Sequence Data, Response Elements,
Affiliations: *** IBB - CNR ***
Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy
Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 80147 Naples, Italy
Department of Pharmacy, University of Naples Federico II, 80134 Naples, Italy
Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy
References: Not available.
SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements
Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein contributing to genome stability via repair of DNA lesions via the base excision repair pathway. It also plays a role in gene expression regulation and RNA metabolism. Another, poorly characterized function is its ability to bind to negative calcium responsive elements (nCaRE) of some gene promoters. The presence of many functional nCaRE sequences regulating gene transcription can be envisioned, given their conservation within ALU repeats. To look for functional nCaRE sequences within the human genome, we performed bioinformatic analyses and identified 57 genes potentially regulated by APE1. We focused on sirtuin-1 (SIRT1) deacetylase due to its involvement in cell stress, including senescence, apoptosis, and tumorigenesis, and its role in the deacetylation of APE1 after genotoxic stress. The human SIRT1 promoter presents two nCaRE elements stably bound by APE1 through its N-terminus. We demonstrate that APE1 is part of a multiprotein complex including hOGG1, Ku70, and RNA Pol II, which is recruited on SIRT1 promoter to regulate SIRT1 gene functions during early response to oxidative stress. These findings provide new insights into the role of nCaRE sequences in the transcriptional regulation of mammalian genes.
SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements