High-resolution cryo-EM structures of TFIIH and their functional implications

Curr Opin Struct Biol. 2019 Dec:59:188-194. doi: 10.1016/j.sbi.2019.08.002. Epub 2019 Oct 7.


Eukaryotic transcription factor IIH (TFIIH) is a 500 kDa-multiprotein complex that harbors two SF2-family DNA-dependent ATPase/helicase subunits and the kinase activity of Cyclin-dependent kinase 7. TFIIH serves as a general transcription factor for transcription initiation by eukaryotic RNA polymerase II and plays an important role in nucleotide excision DNA repair. Aiming to understand the molecular mechanisms of its function and regulation in two key cellular pathways, the high-resolution structure of TFIIH has been pursued for decades. Recent breakthroughs, largely enabled by methodological advances in cryo-electron microscopy, have finally revealed the structure of TFIIH and its interactions in the context of the Pol II-pre-initiation complex, and provide a first glimpse of a TFIIH-containing assembly in DNA repair. Here, we review and discuss these recent structural insights and their functional implications.

Publication types

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

MeSH terms

  • Cryoelectron Microscopy*
  • DNA / chemistry
  • DNA / metabolism
  • DNA Repair
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Quantitative Structure-Activity Relationship*
  • Transcription Factor TFIIH / chemistry*
  • Transcription Factor TFIIH / metabolism*
  • Transcription Factor TFIIH / ultrastructure*
  • Transcription, Genetic
  • Xeroderma Pigmentosum Group A Protein / chemistry
  • Xeroderma Pigmentosum Group A Protein / metabolism


  • XPA protein, human
  • Xeroderma Pigmentosum Group A Protein
  • Transcription Factor TFIIH
  • DNA