Bad Smells and Broken DNA: A Tale of Sulfur-Nucleic Acid Cooperation

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter that exerts numerous physiologic and pathophysiologic effects. Recently, a role for H2S in DNA repair has been identified, where H2S modulates cell cycle checkpoint responses, the DNA damage response (DDR), and mitochondrial and nuclear genomic stability. In addition, several DNA repair proteins modulate cellular H2S concentrations and cellular sulfur metabolism and, in turn, are regulated by cellular H2S concentrations. Many DDR proteins are now pharmacologically inhibited in targeted cancer therapies. As H2S and the enzymes that synthesize it are increased in many human malignancies, it is likely that H2S synthesis inhibition by these therapies is an underappreciated aspect of these cancer treatments. Moreover, both H2S and DDR protein activities in cancer and cardiovascular diseases are becoming increasingly apparent, implicating a DDR–H2S signaling axis in these pathophysiologic processes. Taken together, H2S and DNA repair likely play a central and presently poorly understood role in both normal cellular function and a wide array of human pathophysiologic processes. Here, we review the role of H2S in DNA repair.

Emerging roles of cystathionine β-synthase in various forms of cancer

“…In the physiological context, however, the role of H 2 S in regulating DNA integrity is markedly different, and H 2 S can, in fact, promote various pathways of DNA repair, both in the nuclear DNA and in the mitochondrial DNA. With respect to nuclear DNA repair, the underlying mechanisms may include the activation of ataxia telangiectasia-mutated and Rad3-related (ATR) serine/threonine kinase as well as the regulation of MEK1, PARP1 and ATM [ 325 , [342] , [343] , [344] ]. (Please note that these mechanisms have been characterized in a variety of cell types, not only in cancer cells, and the H 2 S used was often exogenously provided and not endogenously produced.)…”

Fusobacterium nucleatum and its metabolite hydrogen sulfide alter gut microbiota composition and autophagy process and promote colorectal cancer progression

“…H 2 S has long been considered to be harmful to the body, and in recent years, its twofold nature has been continuously reported. On the one hand, H 2 S protects bacteria from host immune system attack and is involved in the DNA damage response ( 18 , 19 ); however, on the other hand, it also has antioxidant effect, mitochondrial protection, and ion channel regulation functions ( 20 , 21 ). The approximate concentration of H 2 S in the human colon has been reported to be 250 µmol/L ( 22 ), and the concentration of H 2 S in the colon has also been reported to be 0.3–3.4 mmol/L or 0.1–2.0 mmol/L ( 23 ).…”