Fig. 6. Schematic of NER, BER, and MMR. (A) gg-NER begins with recognition of a helix-distorting lesion by XPC/HR23B/CETN2, which recruits TFIIH to unwind DNA around the lesion. RPA binds the undamaged ssDNA strand, while XPA/XPF/ERCC1 recognizes the damage and, along with XPG associated with TFIIH, cuts DNA fragment around the lesion. A polymerase fills the gap and XRCC1-Lig3 ligates the newly synthesized DNA. (B) BER. One of 11 DNA glycosylases recognizes DNA damage and excises modified base, creating abasic site. In the short-patch BER, APE1 nicks DNA next to abasic site, and Polβ fills a single nucleotide gap and removes abasic sugar by its dRP lyase activity. In the long-parch BER. Polβ or Polδ/ε synthetizes longer DNA stretch, creating a flap removed by FEN1. The final nick is sealed by XRCC1-Lig3 or Lig1. (C) MMR. A mismatch or a deletion-insertion loop is recognized by MutSα or MutSβ. MutL binds MutS and recruits Exo1, which excises the mismatch. The gap is filled by Polδ and nick ligated by Lig1.