Cha H.,Georgetown University |
Cha H.,CHA Medical University |
Cha H.,John ttle Center For The Radiation Science And Environmental Health |
Lowe J.M.,Georgetown University |
And 7 more authors.
Cancer Research | Year: 2010
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. ©2010 AACR.
Hyduke D.R.,Georgetown University |
Hyduke D.R.,John ttle Center For The Radiation Science And Environmental Health |
Hyduke D.R.,University of California at San Diego |
Laiakis E.C.,Georgetown University |
And 5 more authors.
International Journal of Bioinformatics Research and Applications | Year: 2013
Abstract: Ionising radiation is a pleiotropic stress agent that may induce a variety of adverse effects. Molecular biomarker approaches possess promise to assess radiation exposure, however, the pleiotropic nature of ionizing radiation induced transcriptional responses and the historically poor inter-laboratory performance of omics-derived biomarkers serve as barriers to identification of unequivocal biomarker sets. Here, we present a whole-genome survey of the murine transcriptomic response to physiologically relevant radiation doses, 2 Gy and 8 Gy. We used this dataset with the Random Forest algorithm to correctly classify independently generated data and to identify putative metabolite biomarkers for radiation exposure. Copyright © 2013 Inderscience Enterprises Ltd.