한빛사 논문
- 조회328
Hyukjin Cha1,2,5, Julie M. Lowe1, Henghong Li1,5, Ji-Seon Lee2, Galina I. Belova3, Dmitry V. Bulavin4, and Albert J. Fornace, Jr.1,5
1Department of Biochemistry and Molecular & Cellular Biology and Department of Oncology, Georgetown University, Washington, District of Columbia;
2CHA University, Department of Bio-medical Sciences, Cha Stem Cell Institute, Seoul, Korea;
3NeuroOncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland;
4Institute of Molecular and Cell Biology, Singapore, Singapore;
5John B. Little Center for the Radiation Sciences and Environmental Health, Harvard School of Public Health, Boston, Massachusetts
H. Cha and J.M. Lowe are co–first authors.
Corresponding Authors: Albert J. Fornace, Jr. and Hyukjin Cha
Abstract
The integrity of DNA is constantly challenged throughout the life of a cell by both endogenous and exogenous stresses. A well-organized rapid damage response and proficient DNA repair, therefore, become critically important for maintaining genomic stability and cell survival. When DNA is damaged, the DNA damage response (DDR) can be initiated by alterations in chromosomal structure and histone modifications, such as the phosphorylation of the histone H2AX (the phosphorylated form is referred to as γ-H2AX). γ-H2AX plays a crucial role in recruiting DDR factors to damage sites for accurate DNA repair. On repair completion, γ-H2AX must then be reverted to H2AX by dephosphorylation for attenuation of the DDR. Here, we report that the wild-type p53–induced phosphatase 1 (Wip1) phosphatase, which is often overexpressed in a variety of tumors, effectively dephosphorylates γ-H2AX in vitro and in vivo. Ectopic expression of Wip1 significantly reduces the level of γ-H2AX after ionizing as well as UV radiation. Forced premature dephosphorylation of γ-H2AX by Wip1 disrupts recruitment of important DNA repair factors to damaged sites and delays DNA damage repair. Additionally, deletion of Wip1 enhances γ-H2AX levels in cells undergoing constitutive oncogenic stress. Taken together, our studies show that Wip1 is an important mammalian phosphatase for γ-H2AX and shows an additional mechanism for Wip1 in the tumor surveillance network.
논문정보
- Research article
- 2010년 05월 (BRIC 등록일 2022-12-15)
- 국내(교신)+국외 연구진
- 의약학 > 약학
- 120회 이상 인용된 논문
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