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The p53-inducible gene 3 (PIG3) contributes to early cellular response to DNA damage

Cited 51 time in Web of Science Cited 54 time in Scopus
Authors
Lee, J-H; Kang, Y.; Khare, V.; Jin, Z-Y; Yoon, Y.; Chung, M-H; Jun, J. Y.; You, H. J.; Chang, I-Y; Cho, S-I; Hyun, J-W; Kang, M-Y
Issue Date
2010-03
Publisher
NATURE PUBLISHING GROUP
Citation
ONCOGENE; Vol.29 10; 1431-1450
Keywords
PIG3DNA damage responseDNA damage checkpointDNA repairgamma-H2AX
Abstract
The p53-inducible gene 3 (PIG3) is originally isolated as a p53 downstream target gene, but its function remains unknown. Here, we report a role of PIG3 in the activation of DNA damage checkpoints, after UV irradiation or radiomimetic drug neocarzinostatin (NCS). We show that depletion of endogenous PIG3 sensitizes cells to DNA damage agents, and impaired DNA repair. PIG3 depletion also allows for UV- and NCS-resistant DNA synthesis and permits cells to progress into mitosis, indicating that PIG3 knockdown can suppress intra-S phase and G2/M checkpoints. PIG3-depleted cells show reduced Chk1 and Chk2 phosphorylation after DNA damage, which may directly contribute to checkpoint bypass. PIG3 exhibited diffuse nuclear staining in the majority of untreated cells and forms discrete nuclear foci in response to DNA damage. PIG3 colocalizes with gamma-H2AX and 53BP1 to sites of DNA damage after DNA damage, and binds to a gamma-H2AX. Notably, PIG3 depletion decreases the efficient induction and maintenance of H2AX phosphorylation after DNA damage. Moreover, PIG3 contributes to the recruitment of 53BP1, Mre11, Rad50 and Nbs1 to the sites of DNA break lesions in response to DNA damage. Our combined results suggest that PIG3 is a critical component of the DNA damage response pathway and has a direct role in the transmission of the DNA damage signal from damaged DNA to the intra-S and G2/M checkpoint machinery in human cells. Oncogene (2010) 29, 1431-1450; doi:10.1038/onc.2009.438; published online 21 December 2009
ISSN
0950-9232
Language
English
URI
http://hdl.handle.net/10371/78079
DOI
https://doi.org/10.1038/onc.2009.438
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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