11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway.

      1 , ,
      Current biology : CB
      Elsevier BV

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Genome stability requires that genomic DNA is replicated only once per cell cycle. The replication-licensing system ensures that the formation of prereplicative complexes is temporally separated from the initiation of DNA replication [1-4]. The replication-licensing factors Cdc6 and Cdt1 are required for the assembly of prereplicative complexes during G1 phase. During S phase, metazoan Cdt1 is targeted for degradation by the CUL4 ubiquitin ligase [5-8], and vertebrate Cdc6 is translocated from the nucleus to the cytoplasm [9, 10]. However, because residual vertebrate Cdc6 remains in the nucleus throughout S phase [10-13], it has been unclear whether Cdc6 translocation to the cytoplasm prevents rereplication [1, 2, 14]. The inactivation of C. elegans CUL-4 is associated with dramatic levels of DNA rereplication [5]. Here, we show that C. elegans CDC-6 is exported from the nucleus during S phase in response to the phosphorylation of multiple CDK sites. CUL-4 promotes the phosphorylation and subsequent translocation of CDC-6 via negative regulation of the CDK-inhibitor CKI-1. Rereplication can be induced by coexpression of nonexportable CDC-6 with nondegradable CDT-1, indicating that redundant regulation of CDC-6 and CDT-1 prevents rereplication. This demonstrates that CDC-6 translocation is critical for preventing rereplication and that CUL-4 independently controls both replication-licensing factors.

          Related collections

          Author and article information

          Journal
          Curr Biol
          Current biology : CB
          Elsevier BV
          0960-9822
          0960-9822
          Jun 05 2007
          : 17
          : 11
          Affiliations
          [1 ] Department of Cellular Biology, University of Georgia, Athens, Georgia 30602-2607, USA.
          Article
          S0960-9822(07)01335-8 NIHMS25356
          10.1016/j.cub.2007.04.055
          1945017
          17509881
          d4a46cbf-832f-421b-b1e7-5806e56178a4
          History

          Comments

          Comment on this article