p21(Cip1/WAF1/Sdi1) does not affect expression of base excision DNA repair enzymes during chronic oxidative stress.
Exposure to chronic oxidative stress during elevated oxygen (hyperoxia) damages DNA and inhibits cell proliferation in G(1) through induction of the cyclin-dependent kinase inhibitor p21. Cells that fail to express p21 growth-arrest in S phase. The observation that growth arrest in G(1) is associated with reduced DNA damage and enhanced survival suggests that p21 may affect expression of base excision repair (BER) enzymes used to repair oxidized DNA. This hypothesis was tested in p21 wild-type and p21-deficient mice and human lung adenocarcinoma H1299 cells with tetracycline-on regulated expression of p21. The mRNA levels of Ogg1, Tdg, Udg, Mpg, Nth1, and Mgmt remained constant during 3 days of hyperoxia. The expression of Ogg1, Nth1, and APE protein also remained unchanged. Although hyperoxia increased p21, its absence did not significantly affect expression of these repair enzymes. These findings reveal that hyperoxia induces p21 without significantly altering BER enzyme expression. This suggests that p21 may protect oxidized cells by affecting the activity of BER enzymes and/or through other mechanisms, such as apoptosis.
O'reilly
Michael A
MA
Department of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA. michael_oreilly@urmc.rochester.edu
Vitiello
Peter F
PF
Gehen
Sean C
SC
Staversky
Rhonda J
RJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018496:Hyperoxia / Q000201:enzymology / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D045643:DNA Repair Enzymes