DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway

M A Kang; E-Y So; A L Simons; D R Spitz; T Ouchi

doi:10.1038/cddis.2011.134

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DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway

Journal article

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DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway

M A Kang, E-Y So, A L Simons, D R Spitz and T Ouchi

Cell death & disease, Vol.3(1), pp.e249-e249

01/2012

DOI: 10.1038/cddis.2011.134

PMCID: PMC3270268

PMID: 22237206

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Abstract

The DNA damage response (DDR) cascade and ROS (reactive oxygen species) signaling are both involved in the induction of cell death after DNA damage, but a mechanistic link between these two pathways has not been clearly elucidated. This study demonstrates that ROS induction after treatment of cells with neocarzinostatin (NCS), an ionizing radiation mimetic, is at least partly mediated by increasing histone H2AX. Increased levels of ROS and cell death induced by H2AX overexpression alone or DNA damage leading to H2AX accumulation are reduced by treating cells with the antioxidant N-Acetyl-L-Cysteine (NAC), the NADP(H) oxidase (Nox) inhibitor DPI, expression of Rac1N17, and knockdown of Nox1, but not Nox4, indicating that induction of ROS by H2AX is mediated through Nox1 and Rac1 GTPase. H2AX increases Nox1 activity partly by reducing the interaction between a Nox1 activator NOXA1 and its inhibitor 14-3-3zeta. These results point to a novel role of histone H2AX that regulates Nox1-mediated ROS generation after DNA damage.

H2AX

Rac1

Original

DNA damage

ROS

Nox1

Details

Title: Subtitle: DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway
Creators: M A Kang - , Evanston, IL 60201
E-Y So - , Evanston, IL 60201
A L Simons - , Iowa City, IA 52242
D R Spitz - , Iowa City, IA 52242
T Ouchi - , Evanston, IL 60201
Resource Type: Journal article
Publication Details: Cell death & disease, Vol.3(1), pp.e249-e249
DOI: 10.1038/cddis.2011.134
PMID: 22237206
PMCID: PMC3270268
NLM abbreviation: Cell Death Dis
ISSN: 2041-4889
eISSN: 2041-4889
Publisher: Nature Publishing Group
Alternative title: H2AX regulation of ROS production
Language: English
Date published: 01/2012
Academic Unit: Oral Pathology, Radiology and Medicine; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984047691902771

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