TAILIEUCHUNG - Báo cáo khoa học: 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

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. | ềFEBS Journal 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 Andrey Kropotov1 2 3 Vladimir Serikov1 Jung Suh1 Alexandra Smirnova2 Vladimir Bashkirov4 Boris Zhivotovsky3 and Nikolai Tomilin1 2 1 Children s HospitalOakland Research Institute CA USA 2 Institute of Cytology Russian Academy of Sciences St Petersburg Russia 3 Institute of EnvironmentalMedicine Division of Toxicology Karolinska Institutet Stockholm Sweden 4 Applied Biosystems Foster City CA USA Keywords heterochromatin oxidative stress 8-oxoguanine peroxiredoxin V transcription Correspondence N. V. Tomilin Institute of Cytology Russian Academy of Sciences 194064 St Petersburg Russia Fax 7 812 2470341 Tel 7 812 2475512 E-mail nvtom@ Received 20 March 2006 accepted 10 April 2006 doi 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

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