XPC beyond nucleotide excision repair and skin cancers

Xeroderma pigmentosum group C (XPC) has been known as a DNA damage recognition factor of bulky adducts and as an initiator of global genome nucleotide excision repair (GG-NER). XP-C patients have been shown to have a predisposition to develop skin and certain internal cancers. Recent studies have shown that XPC presents several functional and molecular interactions with fundamental players in several other DNA repair pathways including base excision repair (BER). Furthermore, novel clues indicate that XPC is involved in transcription regulation in the cell. In this review, association between abnormal XPC activity as well as several XPC polymorphisms with the incidence of non-skin tumors is discussed. We also review the current literature regarding the roles of XPC in different DNA repair pathways, highlighting its tumor suppressor activity that may occur independently of its conventional function in NER. Deciphering the NER-independent involvement of XPC in onset and progress of non-skin cancers will have positive implications on prognosis and therapy of cancers with XPC deficiency.