An Overview of DNA Repair in Amyotrophic Lateral Sclerosis

Figure 1

Diagram illustrating the DNA base excision repair (BER) pathway. In this pathway, a DNA glycosylase catalyzes the removal of a damaged base, creating an abasic (AP) site. The APEX1 endonuclease catalyzes the incision of the DNA backbone leaving behind a 5′-deoxyribose phosphate (5′dRP, indicated with a black circle). In short-patch BER, polymerase β (Pol β) displaces the AP site and polymerizes DNA to fill in the gap. Pol β then catalyzes the removal of the displaced AP site, and the ligase III/XRCC1 complex seals the ends. If the 5′dRP is refractory to the action of Pol β, then an additional synthesis of DNA (long-patch BER) is required to displace the modified 5′-sugar phosphate as part of a flap (in grey), which is then removed by flap endonuclease (FEN1). Pol β adds the first nucleotide into the gap and is substituted by polymerase δ/ε which continues long-patch BER. DNA ligase I (LIG1) completes the long-patch pathway.