PMID:21891782

Citation	Zaika, E, Wei, J, Yin, D, Andl, C, Moll, U, El-Rifai, W and Zaika, AI (2011) p73 protein regulates DNA damage repair. FASEB J. 25:4406-14
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.
Links	PubMed PMC3236618 Online version:10.1096/fj.11-192815
Keywords	Animals; Base Sequence; Bile Acids and Salts/toxicity; Cells, Cultured; DNA Damage; DNA Glycosylases/genetics; DNA Primers/genetics; DNA Repair/genetics; DNA Repair/physiology; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Esophageal Neoplasms/etiology; Gastroesophageal Reflux/complications; Gastroesophageal Reflux/genetics; Gastroesophageal Reflux/metabolism; Humans; Mice; Models, Biological; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Tumor Suppressor Proteins/deficiency; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/metabolism; Uracil-DNA Glycosidase/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:P73		GO:0006281: DNA repair	ECO:0000315:		P		Figure 4a. Loss of p73 results in increased DNA damage.	complete CACAO 3917

References

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