Related Experiment Video
Updated: May 29, 2026
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
p73 protein regulates DNA damage repair
Elena Zaika1, Jinxiong Wei, Dengping Yin
1Department of Surgery, Vanderbilt University Medical Center, 1255 Light Hall, 2215 Garland Ave., Nashville, TN 37232, USA.
Summary
p73 protein is crucial for DNA repair during acid-induced damage in the esophagus, unlike p53 and p63. This finding highlights p73
Area of Science:
- Molecular Biology
- Oncology
- Gastroenterology
Background:
- The p53 tumor suppressor is well-studied, but the roles of p73 and p63 are less understood.
- Gastric reflux in the esophagus can lead to pathological conditions involving bile acids and acidic environments.
- These conditions are linked to the progression of esophageal adenocarcinoma.
Purpose of the Study:
- To investigate the role of p73 in the DNA damage response under pathological conditions caused by bile acids.
- To identify specific DNA repair mechanisms regulated by p73 in response to acid and bile acid exposure.
Main Methods:
- Exposure of normal cells to bile acids in acidic conditions.
- Analysis of p53 family protein activation (p73, p53, p63) and c-Abl kinase dependency.
- Utilizing a human DNA repair PCR array to identify affected genes.
- Investigating base excision repair glycosylases (SMUG1, MUTYH).
- Employing mouse models and cell cultures to assess DNA damage in p73-deficient conditions.
Main Results:
- p73 protein is selectively activated in response to bile acid and acid exposure, while p53 and p63 are not.
- Activated p73 induces DNA damage repair, regulating multiple DNA repair genes.
- SMUG1 and MUTYH glycosylases are transcriptionally regulated by p73.
- p73 deficiency leads to increased DNA damage in a mouse model.
Conclusions:
- p73 plays a predominant role in the DNA damage response to bile acid and acid exposure in esophageal conditions.
- p73 regulates key DNA repair pathways, including base excision repair.
- These findings reveal a critical function for p73 in protecting against DNA damage relevant to esophageal adenocarcinoma development.
Related Concept Videos
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:38Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
Overview