Transcriptional regulation of human DNA repair genes following genotoxic stress: trigger mechanisms, inducible responses and genotoxic adaptation
Open Access
- 27 July 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 41 (18), 8403-8420
- https://doi.org/10.1093/nar/gkt635
Abstract
DNA repair is the first barrier in the defense against genotoxic stress. In recent years, mechanisms that recognize DNA damage and activate DNA repair functions through transcriptional upregulation and post-translational modification were the focus of intensive research. Most DNA repair pathways are complex, involving many proteins working in discrete consecutive steps. Therefore, their balanced expression is important for avoiding erroneous repair that might result from excessive base removal and DNA cleavage. Amelioration of DNA repair requires both a fine-tuned system of lesion recognition and transcription factors that regulate repair genes in a balanced way. Transcriptional upregulation of DNA repair genes by genotoxic stress is counteracted by DNA damage that blocks transcription. Therefore, induction of DNA repair resulting in an adaptive response is only visible through a narrow window of dose. Here, we review transcriptional regulation of DNA repair genes in normal and cancer cells and describe mechanisms of promoter activation following genotoxic exposures through environmental carcinogens and anticancer drugs. The data available to date indicate that 25 DNA repair genes are subject to regulation following genotoxic stress in rodent and human cells, but for only a few of them, the data are solid as to the mechanism, homeostatic regulation and involvement in an adaptive response to genotoxic stress.Keywords
This publication has 190 references indexed in Scilit:
- TAp63γ enhances nucleotide excision repair through transcriptional regulation of DNA repair genesDNA Repair, 2012
- Human monocytes are severely impaired in base and DNA double-strand break repair that renders them vulnerable to oxidative stressProceedings of the National Academy of Sciences of the United States of America, 2011
- ATR Autophosphorylation as a Molecular Switch for Checkpoint ActivationMolecular Cell, 2011
- Delayed c-Fos activation in human cells triggers XPF induction and an adaptive response to UVC-induced DNA damage and cytotoxicityCellular and Molecular Life Sciences, 2010
- The DNA Damage Response: Making It Safe to Play with KnivesMolecular Cell, 2010
- TREX1 acts in degrading damaged DNA from drug-treated tumor cellsDNA Repair, 2009
- CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic responseThe EMBO Journal, 2008
- Integrating cell-signalling pathways with NF-κB and IKK functionNature Reviews Molecular Cell Biology, 2007
- Comparison of gene expression changes induced in mouse and human cells treated with direct‐acting mutagensEnvironmental and Molecular Mutagenesis, 2004
- DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociationNature, 2003