Abstract
DNA helicases are essential components of the cellular machinery for DNA replication, recombination, repair, and transcription. The XPD and FancJ proteins are related helicases involved in the nucleotide excision repair (NER) and Fanconi anemia repair pathways, respectively. We demonstrate that both proteins have a conserved domain near the N terminus that includes an iron-sulfur (Fe-S) cluster. Three absolutely conserved cysteine residues provide ligands for the Fe-S cluster, which is essential for the helicase activity of XPD. Yeast strains harboring mutations in the Fe-S domain of Rad3 (yeast XPD) are defective in excision repair of UV photoproducts. Clinically relevant mutations in patients with trichothiodystrophy (TTD) and Fanconi anemia disrupt the Fe-S clusters of XPD and FancJ and thereby abolish helicase activity.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / chemistry
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Amino Acid Sequence
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Archaeal Proteins / chemistry*
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Archaeal Proteins / genetics
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Archaeal Proteins / metabolism
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Conserved Sequence
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DNA Helicases / chemistry
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DNA Helicases / genetics
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DNA Helicases / metabolism
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DNA Repair
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DNA Repair Enzymes / chemistry*
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DNA Repair Enzymes / genetics
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DNA Repair Enzymes / metabolism
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Escherichia coli / genetics
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Fanconi Anemia Complementation Group Proteins / chemistry*
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Fanconi Anemia Complementation Group Proteins / genetics
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Fanconi Anemia Complementation Group Proteins / metabolism
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Iron-Sulfur Proteins / chemistry*
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Iron-Sulfur Proteins / genetics
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Iron-Sulfur Proteins / metabolism
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Models, Molecular
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Molecular Sequence Data
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae / radiation effects
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Saccharomyces cerevisiae Proteins
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Sequence Alignment
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Sulfolobus acidocaldarius / enzymology
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Sulfolobus acidocaldarius / genetics
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Ultraviolet Rays
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Xeroderma Pigmentosum Group D Protein / chemistry*
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Xeroderma Pigmentosum Group D Protein / genetics
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Xeroderma Pigmentosum Group D Protein / metabolism
Substances
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Archaeal Proteins
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Fanconi Anemia Complementation Group Proteins
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Iron-Sulfur Proteins
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Saccharomyces cerevisiae Proteins
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Adenosine Triphosphatases
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Rad3 protein, S cerevisiae
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DNA Helicases
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Xeroderma Pigmentosum Group D Protein
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DNA Repair Enzymes