Hydrogen sulfide and DNA repair

• Published in: Redox biology 2021-01, Vol.38, p.101675-101675, Article 101675
• Main Authors: Shackelford, Rodney, Ozluk, Ekin, Islam, Mohammad Z., Hopper, Brian, Meram, Andrew, Ghali, Ghali, Kevil, Christopher G.
• Format: Article
• Language: English
• Subjects: 3-MST; Animals; Ataxia Telangiectasia Mutated Proteins - genetics; Ataxia Telangiectasia Mutated Proteins - metabolism; ATR; CBS; Cell Cycle Proteins - metabolism; CSE; DNA Damage; DNA damage Response; DNA Repair; H2S; Humans; Hydrogen Sulfide; Phosphorylation; Review
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2020.101675

Recent evidence has revealed that exposing cells to exogenous H 2 S or inhibiting cellular H 2 S synthesis can modulate cell cycle checkpoints, DNA damage and repair, and the expression of proteins involved in the maintenance of genomic stability, all suggesting that H 2 S plays an important role in the DNA damage response (DDR). Here we review the role of H 2 S in the DRR and maintenance of genomic stability. Treatment of various cell types with pharmacologic H 2 S donors or cellular H 2 S synthesis inhibitors modulate the G 1 checkpoint, inhibition of DNA synthesis, and cause p21, and p53 induction. Moreover, in some cell models H 2 S exposure induces PARP-1 and g-H2AX foci formation, increases PCNA, CHK2, Ku70, Ku80, and DNA polymerase-d protein expression, and maintains mitochondrial genomic stability. Our group has also revealed that H 2 S bioavailability and the ATR kinase regulate each other with ATR inhibition lowering cellular H 2 S concentrations, whereas intracellular H 2 S concentrations regulate ATR kinase activity via ATR serine 435 phosphorylation. In summary, these findings have many implications for the DDR, for cancer chemotherapy, and fundamental biochemical metabolic pathways involving H 2 S. •Inhibition of the ATR kinase lowers intracellular H2S concentrations.•Inhibition of H2S synthesis activates the ATR kinase and increases its kinase activity.•Inhibition of H2S synthesis combined with low-level oxidative stress increases genomic instability.•These findings may have applications the cancer chemotherapeutics.