p73 protein regulates DNA damage repair

Elena Zaika, Jinxiong Wei, Dengping Yin, Claudia Andl, Ute Moll, Wael El-Rifai, Alexander I. Zaika

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Although the p53 tumor suppressor is relatively well characterized, much less is known about the functions of other members of the p53 family, p73 and p63. Here, we present evidence that in specific pathological conditions caused by exposure of normal cells to bile acids in acidic conditions, p73 protein plays the predominant role in the DNA damage response. These pathological conditions frequently occur during gastric reflux in the human esophagus and are associated with progression to esophageal adenocarcinoma. We found that despite strong DNA damage induced by bile acid exposure, only p73 (but not p53 and p63) is selectively activated in a c-Abl kinase-dependent manner. The activated p73 protein induces DNA damage repair. Using a human DNA repair PCR array, we identified multiple DNA repair genes affected by p73. Two glycosylases involved in base excision repair, SMUG1 and MUTYH, were characterized and found to be transcriptionally regulated by p73 in DNA damage conditions. Using a surgical procedure in mice, which recapitulates bile acid exposure, we found that p73 deficiency is associated with increased DNA damage. These findings were further investigated with organotypic and traditional cell cultures. Collectively our studies demonstrate that p73 plays an important role in the regulation of DNA damage repair.

Original languageEnglish (US)
Pages (from-to)4406-4414
Number of pages9
JournalFASEB Journal
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Keywords

  • Bile acids
  • p53
  • p63

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Zaika, E., Wei, J., Yin, D., Andl, C., Moll, U., El-Rifai, W., & Zaika, A. I. (2011). p73 protein regulates DNA damage repair. FASEB Journal, 25(12), 4406-4414. https://doi.org/10.1096/fj.11-192815