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

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Unrepaired DNA double-stranded breaks (DSBs) are a major cause of genetic instability.
• Cellular microenvironments can experience fluctuations in hydrogen ion concentration (pH).

Purpose of the Study:

• To investigate the impact of suboptimal extracellular pH (pHe) on DNA double-stranded break repair efficiency.
• To determine if suboptimal pHe affects cellular protective mechanisms like senescence or apoptosis.

Main Methods:

• Fibroblast cultures were exposed to bleomycin to induce DNA double-stranded breaks.
• DNA repair efficiency was assessed by monitoring repair foci and H4K16 acetylation levels.
• Chromosomal instability was evaluated.
• Cellular responses including senescence and apoptosis were analyzed at varying pHe levels (7.2 to 6.9).

Main Results:

• DNA double-stranded break repair recovery was less efficient at suboptimal pHe values.
• Persistence of repair foci and reduced H4K16 acetylation indicated impaired repair.
• Chromosomal instability was observed.
• Senescence and apoptosis were not detected, suggesting repair mechanisms were bypassed.

Conclusions:

• Suboptimal extracellular pH significantly impairs DNA double-stranded break repair efficiency.
• This impairment enhances the genotoxicity of DNA breaks, leading to genetic instability.
• The effect occurs independently of senescence or apoptosis induction.