Role of XPD in cellular functions: To TFIIH and beyond

DNA Repair (Amst). 2016 Aug:44:136-142. doi: 10.1016/j.dnarep.2016.05.019. Epub 2016 May 16.

Abstract

XPD, as part of the TFIIH complex, has classically been linked to the damage verification step of nucleotide excision repair (NER). However, recent data indicate that XPD, due to its iron-sulfur center interacts with the iron sulfur cluster assembly proteins, and may interact with other proteins in the cell to mediate a diverse set of biological functions including cell cycle regulation, mitosis, and mitochondrial function. In this perspective, after first reviewing the function and some of the key disease causing variants that affect XPD's interaction with TFIIH and the CDK-activating kinase complex (CAK), we investigate these intriguing cellular roles of XPD and highlight important unanswered questions that provide a fertile ground for further scientific exploration.

Keywords: Cyclin; Dependent kinases; ERCC2/xeroderma pigmentosum D (XPD); Helicases; Iron-sulfur cluster; Mitosis; Spindle pole; TFIIH.

Publication types

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

MeSH terms

  • Cell Cycle
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinase-Activating Kinase
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Damage
  • DNA Repair*
  • Humans
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism
  • Mitochondria / metabolism
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Structure, Secondary
  • Transcription Factor TFIIH / chemistry
  • Transcription Factor TFIIH / genetics
  • Transcription Factor TFIIH / metabolism*
  • Xeroderma Pigmentosum / genetics*
  • Xeroderma Pigmentosum / metabolism
  • Xeroderma Pigmentosum / pathology
  • Xeroderma Pigmentosum Group D Protein / chemistry
  • Xeroderma Pigmentosum Group D Protein / genetics
  • Xeroderma Pigmentosum Group D Protein / metabolism*

Substances

  • Iron-Sulfur Proteins
  • Transcription Factor TFIIH
  • DNA
  • Cyclin-Dependent Kinases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Cyclin-Dependent Kinase-Activating Kinase