Role of XPD in cellular functions: To TFIIH and beyond.
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.
Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: vanhoutenb@upmc.edu.
Bennett Van
BV
Houten
Rudolf-Virchow-Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg, Germany. Electronic address: jochen.kuper@virchow.uni-wuerzburg.de.
Jochen
J
Kuper
Rudolf-Virchow-Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg, Germany. Electronic address: caroline.kisker@virchow.uni-wuerzburg.de.
Caroline
C
Kisker
D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051758:Transcription Factor TFIIH / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D007506:Iron-Sulfur Proteins; D051758:Transcription Factor TFIIH; D004247:DNA; D018844:Cyclin-Dependent Kinases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D000095043:Cyclin-Dependent Kinase-Activating Kinase
Cyclin; Dependent kinases; ERCC2/xeroderma pigmentosum D (XPD); Helicases; Iron-sulfur cluster; Mitosis; Spindle pole; TFIIH