Downregulation of peroxiredoxin V stimulates formation of etoposide-induced double-strand DNA breaks.
Antioxidant protein Peroxiredoxin V (PrxV) is located in mitochondria and peroxisomes but is also present in the nucleus. Here, we show that nuclear PrxV associates with coilin-containing bodies suggesting possible interaction of this protein with transcription complexes. We also studied etoposide-induced phosphorylation of histone H2AX (gamma-H2AX) in human cells in which PrxV activity was downregulated (knockdown, KD-clones) or compromised by overexpression of redox-negative (RD) protein. In KD clones, but not in RD-clones, formation of etoposide-induced gamma-H2AX was increased, indicating that PrxV inhibits conversion of topoisomerase II cleavage complexes into double-strand DNA breaks but this inhibition is not caused by its antioxidant activity.
Kropotov
Andrei V
AV
Institute of Cytology, Russian Academy of Sciences, Tikchoretskii Av.4, 194064 St. Petersburg, Russia.
Grudinkin
Pavel S
PS
Pleskach
Nadezha M
NM
Gavrilov
Boris A
BA
Tomilin
Nikolai V
NV
Zhivotovsky
Boris
B
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D002999:Clone Cells; D003001:Cloning, Molecular; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D017931:DNA Primers; D005047:Etoposide / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms; D009369:Neoplasms; D010544:Peroxidases / Q000235:genetics*; D054464:Peroxiredoxins; D010741:Phospholipases A / Q000235:genetics; D010766:Phosphorylation
D017931:DNA Primers; C468783:H2AX protein, human; D006657:Histones; D005047:Etoposide; D010544:Peroxidases; D054464:Peroxiredoxins; D004257:DNA Polymerase II; D010741:Phospholipases A