What does interallelic complementation tell us about the mechanism of XPD function? Interallelic complementation is most often observed in multimeric proteins with multiple functional domains. Unfortunately, the structure–function relationship between disease-causing mutations and XPD functional domains, including detailed structural information on XPD or even its stoichiometry within TFIIH, remains unknown. However, based on the ability of cell extracts that are defective in two different TFIIH components (XPD and XPB) to complement NER activity in vitro [26], it is likely that TFIIH (or its components) can either multimerise or exchange at least during the NER reaction. Furthermore, XPD is known to be a “loosely bound” subunit of TFIIH [27]. We thus envisage the molecular mechanism of interallelic complementation to involve the exchange of XPD molecules within the TFIIH complex or turnover of TFIIH complexes containing different XPD molecules at the site of DNA damage during the course of the global genome as well as transcription-coupled repair of either UV-induced or endogenous DNA damage.