MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism

Science. 2012 Jul 13;337(6091):243-5. doi: 10.1126/science.1219664. Epub 2012 Jun 7.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / metabolism
  • Cytoplasm / metabolism*
  • DNA / metabolism*
  • DNA Repair
  • DNA Replication
  • Humans
  • Hydrogenase / metabolism
  • Iron-Sulfur Proteins / metabolism*
  • Metallochaperones / metabolism
  • Metalloproteins
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Protein Stability
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Xeroderma Pigmentosum Group D Protein / metabolism


  • CIAO1 protein, human
  • CIAO2B protein, human
  • CIAO3 protein, human
  • Carrier Proteins
  • Iron-Sulfur Proteins
  • MMS19 protein, human
  • MMS19 protein, mouse
  • Metallochaperones
  • Metalloproteins
  • Nuclear Proteins
  • Transcription Factors
  • DNA
  • Hydrogenase
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human