Abstract
The function of many DNA metabolism proteins depends on their ability to coordinate an iron-sulfur (Fe-S) cluster. Biogenesis of Fe-S proteins is a multistep process that takes place in mitochondria and the cytoplasm, but how it is linked to nuclear Fe-S proteins is not known. Here, we demonstrate that MMS19 forms a complex with the cytoplasmic Fe-S assembly (CIA) proteins CIAO1, IOP1, and MIP18. Cytoplasmic MMS19 also binds to multiple nuclear Fe-S proteins involved in DNA metabolism. In the absence of MMS19, a failure to transfer Fe-S clusters to target proteins is associated with Fe-S protein instability and preimplantation death of mice in which Mms19 has been knocked out. We propose that MMS19 functions as a platform to facilitate Fe-S cluster transfer to proteins critical for DNA replication and repair.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Carrier Proteins / metabolism
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Cytoplasm / metabolism*
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DNA / metabolism*
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DNA Repair
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DNA Replication
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Humans
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Hydrogenase / metabolism
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Iron-Sulfur Proteins / metabolism*
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Metallochaperones / metabolism
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Metalloproteins
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Nuclear Proteins / metabolism
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Protein Stability
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Xeroderma Pigmentosum Group D Protein / metabolism
Substances
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CIAO1 protein, human
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CIAO2B protein, human
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CIAO3 protein, human
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Carrier Proteins
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Iron-Sulfur Proteins
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MMS19 protein, human
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MMS19 protein, mouse
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Metallochaperones
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Metalloproteins
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Nuclear Proteins
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Transcription Factors
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DNA
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Hydrogenase
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Xeroderma Pigmentosum Group D Protein
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ERCC2 protein, human