RT Journal Article SR Electronic T1 The complete structure of the human TFIIH core complex JF bioRxiv FD Cold Spring Harbor Laboratory SP 507723 DO 10.1101/507723 A1 Basil Greber A1 Daniel Toso A1 Jie Fang A1 Eva Nogales YR 2019 UL http://biorxiv.org/content/early/2019/01/05/507723.abstract AB Transcription factor IIH (TFIIH) is a heterodecameric protein complex critical for transcription initiation by RNA polymerase II and nucleotide excision DNA repair. The TFIIH core complex is sufficient for its repair functions and harbors the XPB and XPD DNA-dependent ATPase/helicase subunits, which are affected by human disease mutations. Transcription initiation additionally requires the CdK activating kinase subcomplex. Previous structural work has provided only partial insight into the architecture of TFIIH and its interactions within transcription pre-initiation complexes. Here, we present the complete structure of the human TFIIH core complex, determined by phase-plate cryo-electron microscopy at 3.7 Angstroms resolution. The structure uncovers the molecular basis of TFIIH assembly, revealing how the recruitment of XPB by p52 depends on a pseudo-symmetric dimer of homologous domains in these two proteins. The structure also suggests a function for p62 in the regulation of XPD, and allows the mapping of previously unresolved human disease mutations.