MMS19 Links Cytoplasmic Iron-Sulfur Cluster Assembly to DNA Metabolism
MMS19 Links Cytoplasmic Iron-Sulfur Cluster Assembly to DNA Metabolism
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DOI：
10.1126/science.1219664
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发表时间：
2012-07-13
期刊：
影响因子：
56.9
通讯作者：
Boulton, Simon J.
中科院分区：
文献类型：
--
作者：
Gari, Kerstin;Ortiz, Ana Maria Leon;Boulton, Simon J.
许多DNA代谢蛋白的功能取决于它们协调铁硫（Fe-S）簇的能力。铁- s蛋白的生物发生是一个多步骤的过程，发生在线粒体和细胞质中，但它如何与核铁- s蛋白联系尚不清楚。在这里，我们证明MMS19与细胞质Fe-S组装（CIA）蛋白CIAO1、IOP1和MIP18形成复合物。细胞质中MMS19还与参与DNA代谢的多个核Fe-S蛋白结合。在缺乏MMS19的情况下，Fe-S簇转移到靶蛋白的失败与Fe-S蛋白不稳定和MMS19敲除小鼠的着床前死亡有关。我们提出MMS19作为一个平台，促进Fe-S簇转移到DNA复制和修复的关键蛋白质上。
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.