0) Bulky DNA lesions are repaired by NER. (1) In global repair, XPC-RAD23B recognizes the lesion (red X). (2) Helicase complex machinery (TFIIH, XPG, XPA) is recruited by XPC. (3) XPB subunit of TFIIH translocates along the DNA, leading to formation of ssDNA. (4) XPC-RAD23B, whose primary interface is to dsDNA, is released. RPA binds and protects ssDNA on the undamaged strand. (5). XPD captures the ssDNA and uses its ATPase activity to find the lesion. (6) XPF makes the first cut (arrow) in the dsDNA 5’ to the lesion. (7) Polδ, RFC, and PCNA load onto DNA 5’ to the lesion and start DNA synthesis replacing the damaged region. (8) XPG incises the dsDNA 3’ to the lesion (arrow). (9) TFIIH and XPG leave with the damaged strand. (10) To complete repair, DNA ends are rejoined by DNA ligase.