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The Replication Protein Cdc6 Suppresses Centrosome Over-Duplication in a Manner Independent of Its ATPase Activity

  • Kim, Gwang Su (Department of Biological Sciences, Seoul National University) ;
  • Lee, Inyoung (Department of Biological Sciences, Seoul National University) ;
  • Kim, Ji Hun (Department of Biological Sciences, Seoul National University) ;
  • Hwang, Deog Su (Department of Biological Sciences, Seoul National University)
  • Received : 2017.09.08
  • Accepted : 2017.11.07
  • Published : 2017.12.31

Abstract

The Cdc6 protein is essential for the initiation of chromosomal replication and functions as a licensing factor to maintain chromosome integrity. During the S and G2 phases of the cell cycle, Cdc6 has been found to inhibit the recruitment of pericentriolar material (PCM) proteins to the centrosome and to suppress centrosome over-duplication. In this report, we analyzed the correlation between these two functions of Cdc6 at the centrosome. Cdc6 depletion increased the population of cells showing centrosome over-duplication and premature centrosome separation; Cdc6 expression reversed these changes. Deletion and fusion experiments revealed that the 18 amino acid residues (197-214) of Cdc6, which were fused to the Cdc6-centrosomal localization signal, suppressed centrosome over-duplication and premature centrosome separation. Cdc6 mutant proteins that showed defective ATP binding or hydrolysis did not exhibit a significant difference in suppressing centrosome over-duplication, compared to the wild type protein. In contrast to the Cdc6-mediated inhibition of PCM protein recruitment to the centrosome, the independence of Cdc6 on its ATPase activity for suppressing centrosome over-duplication, along with the difference between the Cdc6 protein regions participating in the two functions, suggested that Cdc6 controls centrosome duplication in a manner independent of its recruitment of PCM proteins to the centrosome.

Keywords

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