Protein N-Homocysteinylation and Colorectal Cancer.

High-fat diet is associated with elevated plasma homocysteine (Hcy), and both are linked to cancer. Although Hcy is not a coded amino acid, proteins do carry Hcy modifications formed via a pathway involving methionyl-tRNA synthetase-catalyzed metabolic conversion of Hcy to Hcy-thiolactone. Hcy-thiolactone then chemically reacts with protein lysine residues, affording KHcy-protein. Recently, Wang et al.[1] (Cell Rep. 2018;25:398-412.e6) showed that this pathway promotes colorectal cancer by impairing DNA damage repair.