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. Author manuscript; available in PMC: 2018 Jan 1.
Published in final edited form as: Photochem Photobiol. 2016 Nov 17;93(1):166–177. doi: 10.1111/php.12647

Figure 2.

Figure 2

Schematic model depicting the role of VCP/p97 in the assembly of preincision complex during GG-NER. CRLDDB2 is recruited to DNA lesions situated in chromatin to recruit and support XPC. Arrival of XPC displaces CSN and activates CRLDDB2 to ubiquitinate DDB2 and XPC in a K48-linked ubiquitin chain. XPC ubiquitination enhances damage binding of XPC, which recruits TFIIH and XPA. The K48-polyubiquitinated DDB2 is extracted by VCP/p97, facilitating the arrival of TFIIH and XPA to the lesion. Meanwhile, RNF111 is recruited and mediates a UV-induced SUMO-targeted K63-ubiquitination of XPC. Subsequently, VCP/p97 mediates ubiquitin-dependent extraction of both K48- and K63-ubiquitinated XPC from lesion sites. The departure of XPC in turn facilitates the arrival of XPG and XPF as well as RPA, forming the final preincision complex. The ubiquitinated DDB2 undergoes proteolysis. Whereas, the ubiquitinated XPC is deubiquitinated by USP7, which restores the native state and constitutive levels of XPC.