How two helicases work together within the TFIIH complex, a perspective from structural studies of XPB and XPD helicases

Abstract

Xeroderma pigmentosum group B (XPB) and D (XPD) are two DNA helicases inside the transcription factor TFIIH complex required for both transcription and DNA repair. The importance of these helicases is underscored by the fact that mutations of XPB and XPD cause diseases with extremely high sensitivity to UV-light and high risk of cancer, premature aging, etc. This mini-review focuses on recent developments in both structural and functional characterization of these XP helicases to illustrate their distinguished biological roles within the architectural restriction of the TFIIH complex. In particular, molecular mechanisms of DNA unwinding by these helicases for promoter opening during transcription initiation and bubble-creation around the lesion during DNA repair are described based on the integration of the crystal structures of XPB and XPD helicases into the architecture of the TFIIH complex.

Key words： XPB; XPD; TFIIH; helicase; DNA repair; nucleotide excision repair; transcription

Acknowledgements

I am grateful to John Tainer, in whose laboratory at The Scripps Research Institute I have determined the structures of AfXPB and SaXPD. I would like also to thank the Department of Biochemistry and CNAS (particularly Thomas Baldwin, Richard Debus and Russ Hille) at University of California-Riverside for many supports in establishing my own laboratory. This project has been supported by grants from UCR and the Hellman Fellowship. I apologize to people whose research activities have contributed to our understandings about the topic but are not cited here due to space limitation.

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