Instant Access to the Journals you Need

starting at just $19.99 per month.

Start Your Free Trial

The role of p53 in base excision repair following genotoxic stress

The role of p53 in base excision repair following genotoxic stress


Abstract The p53 tumor suppressor protein is involved in apoptosis and cell cycle checkpoints. We have shown recently that p53 also facilitates base excision repair (BER). To further examine p53 involvement in the regulation of BER we chose to focus on 3-methyladenine DNA glycosylase (3-MeAde DNA glycosylase), the first enzyme acting in the BER pathway. 3-MeAde DNA glycosylase activity was found to be modulated by the p53 protein. This modulation was dependent on the type of genotoxic stress used. γ-Irradiation damage resulted in activation of glycosylase, which was enhanced by p53. Doxorubicin and hydrogen peroxide (H 2 O 2 ) treatment, although inducing p53 stabilization, did not cause the activation of glycosylase. Nitric oxide (NO) resulted in activation of 3-MeAde DNA glycosylase. Surprisingly this activation was down regulated by wild-type p53. The down regulation of 3-MeAde DNA glycosylase activity was due to trans repression of glycosylase mRNA by p53. Furthermore, we found that AP endonuclease (APE) activity was not altered by NO. Our study provides evidence for a possible antimutagenic role for p53 following exposure of cells to NO species. In the absence of p53, NO exposure results in elevation of 3-MeAde DNA glycosylase activity that results in elevation in the number of AP sites in DNA. At the same time, APE activity does not rise and removal of the AP sites is not further processed resulting in a mutator phenotype. When p53 is present, it down regulates the transcription of 3-MeAde DNA glycosylase. This provides a new model by which p53 prevents the creation of a mutator phenotype.
Loading next page...

You're reading a free preview. Subscribe to read or print the entire article.

And millions more from thousands of peer-reviewed journals, starting at just $19.99/month.

Start Your Free Trial

What content is in DeepDyve?

  • Read and share from thousands of the leading scholarly journals from Springer, Elsevier, Nature, IEEE, Wiley-Blackwell and more.
  • All the latest content is available, no embargo periods.

Rent Scholarly Articles?

  • Read the full article in your browser.
  • Each month you can print 20 pages for free.
  • Access all of your rentals from the cloud anywhere you have an internet connection.
  • Beautiful reading experience – Full charts and figures, just like the PDF.
  • Read as much as you'd like - whenever you'd like.

Happy Users

“In one word renting from DeepDyve is FANTASTIC!!! ... 99% of the time I only need access to an article for a month or so, so renting the articles is perfect for me.”

Adam S.

“Thanks for a great service! For an unaffiliated science blogger like myself this is like a dream come true.”

Seppo P.

“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”

Daniel C.

“Let me seize this opportunity and congratulate you on the service you are rendering to the scientific community.”

Joao B.