2. Academic Validation
  3. Fe-S cluster coordination of the chromokinesin KIF4A alters its subcellular localization during mitosis

Fe-S cluster coordination of the chromokinesin KIF4A alters its subcellular localization during mitosis

  • J Cell Sci. 2018 Jun 27;131(12):jcs211433. doi: 10.1242/jcs.211433.
Lilach Ben-Shimon 1,  Viktoria D Paul 2 3,  Galit David-Kadoch 1,  Marina Volpe 1,  Martin Stümpfig 2,  Eckhard Bill 4,  Ulrich Mühlenhoff 2,  Roland Lill 5 3,  Shay Ben-Aroya 6
Affiliations

Affiliations

  • 1 The Nano Center, Building 206 room B-840, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel, 52900.
  • 2 Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35032 Marburg, Germany.
  • 3 LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Hans-Meerwein-Strasse, 35043 Marburg, Germany.
  • 4 Max-Planck-Institut für Chemische Energiekonversion, Stiftstrasse 34-36, 45470 Mülheim-Ruhr, Germany.
  • 5 Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch-Strasse 6, 35032 Marburg, Germany Shay.Ben-Aroya@biu.ac.il lill@staff.uni-marburg.de.
  • 6 The Nano Center, Building 206 room B-840, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel, 52900 Shay.Ben-Aroya@biu.ac.il lill@staff.uni-marburg.de.
PMID: 29848660 DOI: 10.1242/jcs.211433
Abstract

Fe-S clusters act as co-factors of proteins with diverse functions, for example, in DNA repair. Downregulation of the cytosolic iron-sulfur protein assembly (CIA) machinery promotes genomic instability through the inactivation of multiple DNA repair pathways. Furthermore, CIA deficiencies are associated with so far unexplained mitotic defects. Here, we show that CIA2B (also known as FAM96B) and MMS19, constituents of the CIA targeting complex involved in facilitating Fe-S cluster insertion into cytosolic and nuclear target proteins, colocalize with components of the mitotic machinery. Downregulation of CIA2B and MMS19 impairs the mitotic cycle. We identify the chromokinesin KIF4A as a mitotic component involved in these effects. KIF4A binds a Fe-S cluster in vitro through its conserved cysteine-rich domain. We demonstrate in vivo that this domain is required for the mitosis-related KIF4A localization and for the mitotic defects associated with KIF4A knockout. KIF4A is the first identified mitotic component carrying such a post-translational modification. These findings suggest that the lack of Fe-S clusters in KIF4A upon downregulation of the CIA targeting complex contributes to the mitotic defects.

Keywords

Chromokinesin; Fe-S cluster; Genome stability.

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