8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging

Peter German, David Saenz, Peter Szaniszlo, Leopoldo Aguilera-Aguirre, Lang Pan, Muralidhar L. Hegde, Attila Bacsi, Gyorgy Hajas, Zsolt Radak, Xueqing Ba, Sankar Mitra, John Papaconstantinou, Istvan Boldogh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER "wires" senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed -86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

Original languageEnglish (US)
JournalMechanisms of Ageing and Development
DOIs
StateAccepted/In press - Apr 14 2016

Fingerprint

DNA Repair
Lung
Cultured Cells
DNA
DNA Glycosylases
G1 Phase Cell Cycle Checkpoints
Biological Phenomena
Gene Expression
Gene Ontology
1-Phosphatidylinositol 4-Kinase
Monomeric GTP-Binding Proteins
Cell Aging
Diploidy
Mitogens
DNA Damage
Phosphotransferases
Fibroblasts
Health
Genes
8-hydroxyguanine

Keywords

  • 8-oxoguanine
  • Aging
  • OGG1
  • Senescence

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging. / German, Peter; Saenz, David; Szaniszlo, Peter; Aguilera-Aguirre, Leopoldo; Pan, Lang; Hegde, Muralidhar L.; Bacsi, Attila; Hajas, Gyorgy; Radak, Zsolt; Ba, Xueqing; Mitra, Sankar; Papaconstantinou, John; Boldogh, Istvan.

In: Mechanisms of Ageing and Development, 14.04.2016.

Research output: Contribution to journalArticle

German, P, Saenz, D, Szaniszlo, P, Aguilera-Aguirre, L, Pan, L, Hegde, ML, Bacsi, A, Hajas, G, Radak, Z, Ba, X, Mitra, S, Papaconstantinou, J & Boldogh, I 2016, '8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging', Mechanisms of Ageing and Development. https://doi.org/10.1016/j.mad.2016.06.009
German, Peter ; Saenz, David ; Szaniszlo, Peter ; Aguilera-Aguirre, Leopoldo ; Pan, Lang ; Hegde, Muralidhar L. ; Bacsi, Attila ; Hajas, Gyorgy ; Radak, Zsolt ; Ba, Xueqing ; Mitra, Sankar ; Papaconstantinou, John ; Boldogh, Istvan. / 8-Oxoguanine DNA glycosylase1-driven DNA repair-A paradoxical role in lung aging. In: Mechanisms of Ageing and Development. 2016.
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