The essential and multifunctional TFIIH complex

Protein Sci. 2018 Jun;27(6):1018-1037. doi: 10.1002/pro.3424. Epub 2018 Apr 27.

Abstract

TFIIH is a 10-subunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in eukaryotic cells, much progress has been made even in just the past few years, due in part to technological advances (e.g. cryoEM and single molecule methods) and the development of chemical inhibitors of TFIIH enzymes. This review focuses on the major cellular roles for TFIIH, with an emphasis on TFIIH function as a regulator of pol II transcription. We describe the structure of TFIIH and its roles in pol II initiation, promoter-proximal pausing, elongation, and termination. We also discuss cellular roles for TFIIH beyond transcription (e.g. DNA repair, cell cycle regulation) and summarize small molecule inhibitors of TFIIH and diseases associated with defects in TFIIH structure and function.

Keywords: CDK7; Mediator; RNA polymerase II pausing; TFIIE; TFIIH; THZ1; XPB; XPD; transcription; triptolide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Cycle
  • DNA Repair
  • Diterpenes / metabolism*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Epoxy Compounds / metabolism
  • Humans
  • Phenanthrenes / metabolism*
  • Promoter Regions, Genetic
  • RNA Polymerase II / metabolism
  • Transcription Factor TFIIH / chemistry
  • Transcription Factor TFIIH / metabolism*
  • Transcription, Genetic

Substances

  • Diterpenes
  • Enzyme Inhibitors
  • Epoxy Compounds
  • Phenanthrenes
  • Transcription Factor TFIIH
  • triptolide
  • RNA Polymerase II

Associated data

  • PDB/5OF4