Fig. 3.

Role of centrins in nucleotide excision repair pathways. Diagrammatic representation of the pathways of nucleotide excision repair and the roles of centrin within these pathways. DNA lesions induced by UV irradiation are repaired through one of two pathways, global genome repair (GGR) or transcription coupled repair (TCR). During TCR, the initial recognition of DNA damage is achieved through a block in transcription [180]. However, for regions of DNA not being actively transcribed, this recognition relies on the heterotrimer of XPC-HRAD23-centrin 2, aided by the UV-DDB complex for less helical-distorting lesions, such as cyclobutane pyrimidine dimers (CPD) [199]. Centrin 2 localises to the nucleus through SUMOylation by SUMO 2/3, which involves the E3 ligase Polycomb protein 2 [148]. Once in the nucleus, retention of centrin 2 is dependent on its interaction with XPC, as described in the text. After recognition of the DNA lesion, XPC then recruits TFIIH through interaction with one of its subunits, XPB [225]. Helicase activities of TFIIH unwind DNA, and 25–30 base pairs of DNA are excised. The resulting gap is filled by an appropriate polymerase and the damage repaired