8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization

Jixian Luo, Koa Hosoki, Attila Bacsi, Zsolt Radak, Muralidhar L. Hegde, Sanjiv Sur, Tapas Hazra, Allan R. Brasier, Xueqing Ba, Istvan Boldogh

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, whereas its etiological relevance is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair (BER) pathway. OGG1 binds free 8-oxoG and this complex functions as an activator of Ras family GTPases. Here we examined whether OGG1-initiated BER is associated with the activation of Rho GTPase and mediates changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated BER in cultured cells and mouse lungs and used molecular approaches such as active Rho pull-down assays, siRNA ablation of gene expression, immune blotting, and microscopic imaging. We found that OGG1 physically interacts with Rho GTPase and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediates α-smooth muscle actin (α-SMA) polymerization into stress fibers and increases the level of α-SMA in insoluble cellular/tissue fractions. These changes were absent in cells lacking OGG1. These unexpected data and those showing that 8-oxoG repair is a lifetime process suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes and organ remodeling observed in various chronic diseases.

Original languageEnglish (US)
Pages (from-to)430-438
Number of pages9
JournalFree Radical Biology and Medicine
Volume73
DOIs
StatePublished - 2014

Fingerprint

DNA Glycosylases
rho GTP-Binding Proteins
DNA Repair
Polymerization
Smooth Muscle
Muscle
Actins
Repair
Chemical activation
DNA
Cultured Cells
8-hydroxyguanine
Cells
Activator Appliances
Cell signaling
ras Proteins
Lung
Stress Fibers
GTP Phosphohydrolases
Ablation

Keywords

  • Base excision repair
  • Cytoskeleton
  • Free radicals
  • OGG1
  • Rho-GTP
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization. / Luo, Jixian; Hosoki, Koa; Bacsi, Attila; Radak, Zsolt; Hegde, Muralidhar L.; Sur, Sanjiv; Hazra, Tapas; Brasier, Allan R.; Ba, Xueqing; Boldogh, Istvan.

In: Free Radical Biology and Medicine, Vol. 73, 2014, p. 430-438.

Research output: Contribution to journalArticle

Luo, Jixian ; Hosoki, Koa ; Bacsi, Attila ; Radak, Zsolt ; Hegde, Muralidhar L. ; Sur, Sanjiv ; Hazra, Tapas ; Brasier, Allan R. ; Ba, Xueqing ; Boldogh, Istvan. / 8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization. In: Free Radical Biology and Medicine. 2014 ; Vol. 73. pp. 430-438.
@article{8c2d3a3e114c4722ba017cada7e4a05a,
title = "8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization",
abstract = "Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, whereas its etiological relevance is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair (BER) pathway. OGG1 binds free 8-oxoG and this complex functions as an activator of Ras family GTPases. Here we examined whether OGG1-initiated BER is associated with the activation of Rho GTPase and mediates changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated BER in cultured cells and mouse lungs and used molecular approaches such as active Rho pull-down assays, siRNA ablation of gene expression, immune blotting, and microscopic imaging. We found that OGG1 physically interacts with Rho GTPase and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediates α-smooth muscle actin (α-SMA) polymerization into stress fibers and increases the level of α-SMA in insoluble cellular/tissue fractions. These changes were absent in cells lacking OGG1. These unexpected data and those showing that 8-oxoG repair is a lifetime process suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes and organ remodeling observed in various chronic diseases.",
keywords = "Base excision repair, Cytoskeleton, Free radicals, OGG1, Rho-GTP, ROS",
author = "Jixian Luo and Koa Hosoki and Attila Bacsi and Zsolt Radak and Hegde, {Muralidhar L.} and Sanjiv Sur and Tapas Hazra and Brasier, {Allan R.} and Xueqing Ba and Istvan Boldogh",
year = "2014",
doi = "10.1016/j.freeradbiomed.2014.03.030",
language = "English (US)",
volume = "73",
pages = "430--438",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - 8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization

AU - Luo, Jixian

AU - Hosoki, Koa

AU - Bacsi, Attila

AU - Radak, Zsolt

AU - Hegde, Muralidhar L.

AU - Sur, Sanjiv

AU - Hazra, Tapas

AU - Brasier, Allan R.

AU - Ba, Xueqing

AU - Boldogh, Istvan

PY - 2014

Y1 - 2014

N2 - Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, whereas its etiological relevance is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair (BER) pathway. OGG1 binds free 8-oxoG and this complex functions as an activator of Ras family GTPases. Here we examined whether OGG1-initiated BER is associated with the activation of Rho GTPase and mediates changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated BER in cultured cells and mouse lungs and used molecular approaches such as active Rho pull-down assays, siRNA ablation of gene expression, immune blotting, and microscopic imaging. We found that OGG1 physically interacts with Rho GTPase and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediates α-smooth muscle actin (α-SMA) polymerization into stress fibers and increases the level of α-SMA in insoluble cellular/tissue fractions. These changes were absent in cells lacking OGG1. These unexpected data and those showing that 8-oxoG repair is a lifetime process suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes and organ remodeling observed in various chronic diseases.

AB - Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, whereas its etiological relevance is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair (BER) pathway. OGG1 binds free 8-oxoG and this complex functions as an activator of Ras family GTPases. Here we examined whether OGG1-initiated BER is associated with the activation of Rho GTPase and mediates changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated BER in cultured cells and mouse lungs and used molecular approaches such as active Rho pull-down assays, siRNA ablation of gene expression, immune blotting, and microscopic imaging. We found that OGG1 physically interacts with Rho GTPase and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediates α-smooth muscle actin (α-SMA) polymerization into stress fibers and increases the level of α-SMA in insoluble cellular/tissue fractions. These changes were absent in cells lacking OGG1. These unexpected data and those showing that 8-oxoG repair is a lifetime process suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes and organ remodeling observed in various chronic diseases.

KW - Base excision repair

KW - Cytoskeleton

KW - Free radicals

KW - OGG1

KW - Rho-GTP

KW - ROS

UR - http://www.scopus.com/inward/record.url?scp=84905125583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905125583&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2014.03.030

DO - 10.1016/j.freeradbiomed.2014.03.030

M3 - Article

VL - 73

SP - 430

EP - 438

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -