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      A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.

      1 , , , ,
      Molecular cell
      Elsevier BV

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          Abstract

          Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta propeller Ddb1 adaptor protein, but few substrate receptors have been identified. Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. DCAF2/Cdt2, which is related to S. pombe Cdt2, functions in Xenopus egg extracts and human cells to destroy the replication licensing protein Cdt1 in S phase and after DNA damage. Depletion of human Cdt2 causes rereplication and checkpoint activation. In Xenopus, Cdt2 is recruited to replication forks via Cdt1 and PCNA, where Cdt1 ubiquitylation occurs. These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication.

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          Author and article information

          Journal
          Mol Cell
          Molecular cell
          Elsevier BV
          1097-2765
          1097-2765
          Sep 01 2006
          : 23
          : 5
          Affiliations
          [1 ] Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
          Article
          S1097-2765(06)00570-3
          10.1016/j.molcel.2006.08.010
          16949367
          a89ef713-7438-4e39-ac37-cbaf132c1426
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