Abstract
Instability of the nuclear genome is a hallmark of cancer and aging. MMS19 protein has been linked to maintenance of genomic integrity, but the molecular basis of this connection is unknown. Here, we identify MMS19 as a member of the cytosolic iron-sulfur protein assembly (CIA) machinery. MMS19 functions as part of the CIA targeting complex that specifically interacts with and facilitates iron-sulfur cluster insertion into apoproteins involved in methionine biosynthesis, DNA replication, DNA repair, and telomere maintenance. MMS19 thus serves as an adapter between early-acting CIA components and a subset of cellular iron-sulfur proteins. The function of MMS19 in the maturation of crucial components of DNA metabolism may explain the sensitivity of MMS19 mutants to DNA damage and the presence of extended telomeres.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Carrier Proteins / metabolism
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Cytosol / metabolism
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DNA / metabolism*
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DNA Damage
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DNA Repair
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DNA Replication
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DNA, Fungal / metabolism*
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Genomic Instability*
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HeLa Cells
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Humans
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Immunoprecipitation
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Iron / metabolism
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Iron-Sulfur Proteins / metabolism*
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Metallochaperones / metabolism
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Metalloproteins
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Methionine / biosynthesis
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Nuclear Proteins / metabolism
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Protein Interaction Mapping
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Proteomics
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RNA Interference
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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CIAO1 protein, human
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CIAO2B protein, human
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Carrier Proteins
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DNA, Fungal
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Iron-Sulfur Proteins
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MET18 protein, S cerevisiae
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MMS19 protein, human
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Metallochaperones
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Metalloproteins
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Nuclear Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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DNA
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Methionine
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Iron