Figure 1.

Major DNA repair pathways. DNA repair occurs via different pathways involving multiple proteins, among them many are directly NAD⁺ dependent (shaded in orange). Repair of single-strand breaks (SSBs) through base excision repair (BER) involves NAD⁺-consuming PARP1 and PARP2. Double-strand breaks (DSBs) are repaired either through homologous recombination (HR) or nonhomologous end-joining (NHEJ) pathways, facilitated by multiple ARTDs and SIRTs. NAD⁺-dependent enzymes are also implicated in nucleotide excision repair (NER) as well as mismatch repair (MMR) pathways. A potential NAD⁺-dependent role of LIG IV is under discussion (see text for details). ARTD, diphtheria toxin–like ADP-ribosyltransferase; LIG IV, ligase IV; PARP, poly-ADP-ribose polymerase; SIRT, sirtuin.