Suboptimal extracellular pH values alter DNA damage response to induced double-strand breaks.

TitleSuboptimal extracellular pH values alter DNA damage response to induced double-strand breaks.
Publication TypeJournal Article
Year of Publication2018
AuthorsMassonneau J, Ouellet C, Lucien F, Dubois CM, Tyler J, Boissonneault G
JournalFEBS Open Bio
Volume8
Issue3
Pagination416-425
Date Published2018 03
ISSN2211-5463
Abstract

Conditions leading to unrepaired DNA double-stranded breaks are potent inducers of genetic instability. Systemic conditions may lead to fluctuation of hydrogen ions in the cellular microenvironment, and we show that small variations in extracellular pH, termed suboptimal pHe, can decrease the efficiency of DNA repair in the absence of intracellular pH variation. Recovery from bleomycin-induced DNA double-stranded breaks in fibroblasts proceeded less efficiently at suboptimal pHe values ranging from 7.2 to 6.9, as shown by the persistence of repair foci, reduction of H4K16 acetylation, and chromosomal instability, while senescence or apoptosis remained undetected. By allowing escape from these protective mechanisms, suboptimal pHe may therefore enhance the genotoxicity of double-stranded breaks, leading to genetic instability.

DOI10.1002/2211-5463.12384
Alternate JournalFEBS Open Bio
PubMed ID29511618
PubMed Central IDPMC5832969
Grant ListR01 CA095641 / CA / NCI NIH HHS / United States
R01 GM064475 / GM / NIGMS NIH HHS / United States
Related Faculty: 
Jessica K. Tyler, Ph.D.

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