Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum

Cell. 2001 Feb 9;104(3):353-63. doi: 10.1016/s0092-8674(01)00223-9.


Inherited mutations of the TFIIH helicase subunits xeroderma pigmentosum (XP) B or XPD yield overlapping DNA repair and transcription syndromes. The high risk of cancer in these patients is not fully explained by the repair defect. The transcription defect is subtle and has proven more difficult to evaluate. Here, XPB and XPD mutations are shown to block transcription activation by the FUSE Binding Protein (FBP), a regulator of c-myc expression, and repression by the FBP Interacting Repressor (FIR). Through TFIIH, FBP facilitates transcription until promoter escape, whereas after initiation, FIR uses TFIIH to delay promoter escape. Mutations in TFIIH that impair regulation by FBP and FIR affect proper regulation of c-myc expression and have implications in the development of malignancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Cell Line
  • DNA Helicases / metabolism
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique
  • Genes, Dominant
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Proteins / metabolism
  • Mutation
  • Neoplasms / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Recombinant Proteins / metabolism
  • Repressor Proteins / metabolism
  • Transcription Factor TFIIH
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII*
  • Transcription, Genetic
  • Transfection
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / metabolism*


  • DNA-Binding Proteins
  • FUBP1 protein, human
  • Luminescent Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Transcription Factors
  • Transcription Factors, TFII
  • poly-U binding splicing factor 60KDa
  • XPBC-ERCC-3 protein
  • Green Fluorescent Proteins
  • Transcription Factor TFIIH
  • DNA Helicases