Transcription factor II H

Transcription factor II H (TF_IIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TF_IIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named TF_IIH in 1992.^[1][2]

TF_IIH consists of ten subunits, 7 of which (ERCC2/XPD, ERCC3/XPB, GTF2H1/p62, GTF2H4/p52, GTF2H2/p44, GTF2H3/p34 and GTF2H5/TTDA) form the core complex. The cyclin-activating kinase-subcomplex (CDK7, MAT1, and cyclin H) is linked to the core via the XPD protein.^[3] Two of the subunits, ERCC2/XPD and ERCC3/XPB, have helicase and ATPase activities and help create the transcription bubble. In a test tube, these subunits are only required for transcription if the DNA template is not already denatured or if it is supercoiled.

Two other TF_IIH subunits, CDK7 and cyclin H, phosphorylate serine amino acids on the RNA polymerase II C-terminal domain and possibly other proteins involved in the cell cycle. Next to a vital function in transcription initiation, TF_IIH is also involved in nucleotide excision repair.