DNA ligase and DNA primase

DNA ligase and DNA primase are two distinct classes of enzymes essential for DNA replication, repair, and recombination across all domains of life. DNA primase (e.g., PRIM1 in humans) is a specialized RNA polymerase that synthesizes short RNA primers on the single-stranded DNA template, providing the necessary 3-hydroxyl group for DNA polymerase to initiate elongation (UniProt P49642). DNA ligase (e.g., LIG1, LIG3, LIG4 in humans) catalyzes the formation of a phosphodiester bond between the 3-hydroxyl and 5-phosphate ends of DNA fragments, effectively sealing nicks and joining Okazaki fragments during lagging strand synthesis (UniProt P18858). In clinical practice, DNA primase is a validated target for antiviral therapy, particularly through helicase-primase inhibitors like Pritelivir and Amenamevir used to treat Herpes Simplex Virus (HSV) infections (Fielden et al., 2018). DNA ligases are being actively investigated as targets for anti-cancer therapies, where inhibition can lead to the accumulation of DNA damage and apoptosis in rapidly dividing cells, and as targets for novel antibiotics due to the structural differences between bacterial NAD+-dependent ligases and human ATP-dependent ligases (Chen et al., 2015). Because these are two separate enzymes with distinct catalytic roles and structures, they are typically treated as individual therapeutic targets rather than a single entity.

Other names

DNA ligaseDNA primaseDNA nucleotidyltransferase (RNA-primed)Pol-prim complexHelicase-primase complexLIG1PRIM1

Inhibition of RNA primer synthesis by DNA primase and inhibition of phosphodiester bond formation by DNA ligase.