Fig. 3.

Base excision repair (BER) pathway. BER is the major DNA damage repair pathway for correcting non-bulky forms of DNA damage (e.g., deamination, base oxidation or alkylation) that do not significantly distort the DNA helix. This process is performed in a series of successive reactions. A damage specific DNA glycosylase initially detects the lesion and excises the damaged base creating an abasic site (AP site), that is then cleaved by APE1 creating a SSB with 3′-hydroxyl (OH) and 5′-dRP ends. Alternatively, the NEIL1-3 glycosylase generates a 1-nucleotide (nt) gap through βδ-elimination flanked by 3′- and 5′-phosphate ends. The 3′ phosphate is removed by PNKP to produce a 3′-OH end. These DNA ends are processed by one of two sub-pathways: short-patch (single-nucleotide) or long-patch (more than one nucleotide) repair, during which a DNA polymerase fills the gap with the correct nucleotides and the repair mechanism is completed with the sealing of the nick by a DNA ligase. More concretely, the ssDNA nick is recognized by PARP1, which upon auto-PARylation, recruits downstream BER components. In short-patch BER, Polβ excises the dRP and fills the gap with a new nucleotide. The nick is then ligated by XRCC1-LIG3. In long-patch BER, Polδ/ε fill the gap with 2-11 nucleotides, creating a 5’-flap that is excised by FEN1 and finally ligated by LIG1 in a PCNA-dependent manner. Figure created with BioRender