Reference: Gari K, et al. (2012) MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism. Science 337(6091):243-5

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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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Gari K, León Ortiz AM, Borel V, Flynn H, Skehel JM, Boulton SJ
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