title: Constitutive expression of the human peroxiredoxin V gene contributes to protection of the genome from oxidative DNA lesions and to suppression of transcription of noncoding DNA.
abstract: Peroxiredoxins belong to a family of antioxidant proteins that neutralize reactive oxygen species. One member of this family, peroxiredoxin I (PRDX1), suppresses DNA oxidation. Peroxiredoxin V (PRDX5) has been cloned as a transcriptional corepressor, as a peroxisomal/mitochondrial antioxidant protein, and as an inhibitor of p53-dependent apoptosis. Promoters of mammalian PRDX5 genes contain clusters of antioxidant response elements, which can bind the transcription factor NRF2. However, we found that expression of the human PRDX5 gene in situ was not stimulated by the oxidative agent menadione. Silencing of the NRF2 gene in the absence of oxidative stress by specific siRNA did not decrease PRDX5 protein concentration. We also constructed clones of human lung epithelial cells A549 with siRNA-mediated knockdown of the PRDX5 gene. This led to a significant increase in 8-oxoguanine formation in cell DNA. In the PRDX5 knockdown clone, an increase in transcripts containing sequences of alpha-satellite and satellite III DNAs was also detected, suggesting that this protein may be required for silencing of heterochromatin. Together, these results suggest that constitutively expressed PRDX5 gene plays an important role in protecting the genome against oxidation and may also be involved in the control of transcription of noncoding DNA.
authors.affiliation: Children's Hospital Oakland Research Institute, CA, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Kropotov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Serikov
authors.forename: Jung
authors.initials: J
authors.lastname: Suh
authors.forename: Alexandra
authors.initials: A
authors.lastname: Smirnova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bashkirov
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: Nikolai
authors.initials: N
authors.lastname: Tomilin
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D004249:DNA Damage; D004276:DNA, Satellite / Q000235:genetics*; D005786:Gene Expression Regulation; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D004276:DNA, Satellite; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D006151:Guanosine; C046215:8-hydroxyguanosine; D010544:Peroxidases; C515940:PRDX1 protein, human; C515974:PRDX5 protein, human; D054464:Peroxiredoxins