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The ubiquitin ligase complex RBX1:CUL4:DDB1:DTL can also monoubiquitinate PCNA. RBX1:CUL4:DDB1:DTL is probably responsible for the basal monoubiquitination of PCNA and may contribute to the kinetics of DNA-damage induced PCNA monoubiquitination (Terai et al. 2010).
In the absence of DNA damage, the ubiquitin ligase activity of UV-DDB complex is inhibited by association with the COP9 signalosome (CSN complex), which dissociates from the UV-DDB complex upon binding to damaged DNA (Groisman et al. 2003, Fischer et al. 2011). Ubiquitination of XPC by UV-DDB promotes XPC retention at GG-NER sites, while progressive autoubiquitination of UV-DDB promotes the dissociation of UV-DDB from the DNA and may act as an intracellular signal (Sugasawa et al. 2005). The UV-DDB complex also ubiquitinates histones H2A, H3 and H4, which may trigger chromatin remodeling at DNA damage site and regulate the accessibility of damaged DNA to repair factors (Kapetanaki et al. 2006, Wang et al. 2006).
Binding of the XPC:RAD23:CETN2 complex to distorted DNA is enhanced in the presence of the DDB1:DDB2 complex, also known as the UV-DDB complex. The UV-DDB complex preferentially binds UV-generated lesions, such as pyrimidine-pyrimidone photodimers (6-4 PPDs) and cyclobutane pyrimidine dimers (CPDs), but also recognizes DNA with apurinic/apyrimidinic (AP) sites, and 2-3 bp mismatches (Fujiwara et al. 1999, Wittschieben et al. 2005). The DDB2 subunit of the UV-DDB complex is a WD40 repeat beta-propeller protein. The beta-propeller domain of DDB2 binds the damaged DNA strand (Scrima et al. 2008). The UV-DDB complex is part of a larger ubiquitin ligase complex that, besides DDB1 and DDB2, also contains CUL4A or CUL4B and RBX1 (Groisman et al. 2003, Sugasawa et al. 2005). In the case of 6-4 PPDs and CPDs, UV-DDB binding to damaged DNA probably precedes the binding of the XPC:RAD23:CETN2 complex. However, in the case of 6-4 PPDs, the XPC:RAD23:CETN2 complex may also recognize damaged DNA in the absence of the UV-DDB complex (Fitch et al. 2003, Moser et al. 2005, Wang et al. 2004), but the UV-DDB complex may be important for retention of DNA repair proteins at the DNA damage site (Oh et al. 2011).
The INO80 chromatin remodelling complex positively regulates GG-NER. INO80 and ACTR5 (ARP5) subunits of the INO80 complex are enriched at GG-NER sites, probably via interaction with DDB1. Chromatin relaxation by the INO80 complex at DNA damage site may be necessary for XPC recruitment (Jiang et al. 2010). In yeast, the interaction between INO80 and the orthologs of XPC and RAD23 has been reported and it was suggested that this interaction is important for the restoration of chromatin structure after GG-NER completion (Sarkar et al. 2010).