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Published on: June 26, 2020
Involvement of p29 in DNA damage responses and Fanconi anemia pathway
Po-Chen Chu1, Tao-Yeuan Wang, Yen-Ta Lu
1Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Taipei, Taiwan.
Abstract:
Human p29 is a chromatin-associated protein and the silencing of p29 expression increases cell population in G(1) phase and decreases phosphorylation levels of Chk1 and Chk2 in response to UV treatment. To further characterize the function of p29, U2OS and Fanconi anemia complementation group G (FA-G) cells with constitutive p29 expression have been established. Analyses of these cells identified increased phosphorylation levels of Chk1 and Chk2, which were accompanied by elevated amounts of chromatin-associated Mre11-Rad50-Nbs1 complex and ATR-IP. Monoubiquitination of the FA ID complex was restored in p29 stably expressing FA-G cells. Moreover, lower tumor incidence was observed in mp29 transgenic mice after UV irradiation. These results suggest the involvement of p29 in the DNA damage responses and Fanconi anemia pathway.
Insights
Human p29 protein plays a role in DNA damage response and the Fanconi anemia pathway. Silencing p29 affects cell cycle progression, while its expression aids in DNA repair mechanisms and reduces tumor incidence post-UV exposure.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- p29 is a chromatin-associated protein.
- p29's role in DNA damage response and Fanconi anemia pathway requires further elucidation.
Purpose of the Study:
- To characterize the function of human p29 in DNA damage response.
- To investigate p29's involvement in the Fanconi anemia pathway.
Main Methods:
- Established U2OS and Fanconi anemia complementation group G (FA-G) cells with constitutive p29 expression.
- Analyzed Chk1/Chk2 phosphorylation, Mre11-Rad50-Nbs1 complex, ATR-IP, and FA ID complex monoubiquitination.
- Assessed tumor incidence in mp29 transgenic mice after UV irradiation.
Main Results:
- p29 silencing increased G1 phase cell population and decreased Chk1/Chk2 phosphorylation.
- Constitutive p29 expression elevated Chk1/Chk2 phosphorylation, Mre11-Rad50-Nbs1, and ATR-IP.
- p29 expression restored FA ID complex monoubiquitination in FA-G cells and reduced tumor incidence in mice post-UV.
Conclusions:
- p29 is involved in DNA damage responses.
- p29 plays a role in the Fanconi anemia pathway.
- p29 may function as a tumor suppressor in response to UV-induced DNA damage.
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