Report

MMS19 Links Cytoplasmic Iron-Sulfur Cluster Assembly to DNA Metabolism

See allHide authors and affiliations

Science  07 Jun 2012:
1219664
DOI: 10.1126/science.1219664

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Abstract

The function of many DNA metabolism proteins depends on their ability to coordinate an iron-sulfur (FeS) cluster. Biogenesis of FeS proteins is a multistep process that takes place in mitochondria and the cytoplasm, but how it is linked to nuclear FeS proteins is not known. Here, we demonstrate that MMS19 forms a complex with the cytoplasmic FeS assembly (CIA) proteins CIAO1, IOP1, and MIP18. Cytoplasmic MMS19 also binds to multiple nuclear FeS proteins involved in DNA metabolism. In the absence of MMS19, a failure to transfer FeS clusters to target proteins is associated with FeS protein instability and pre-implantation lethality of Mms19 knockout mice. We propose that MMS19 functions as a platform to facilitate FeS cluster transfer to proteins critical for DNA replication and repair.

View Full Text