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First published online December 20, 2006
doi: 10.1242/10.1242/jcs.03327

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C-terminal domains deliver the DNA replication factor Ciz1 to the nuclear matrix

¹ CRISTAL, School of Medicine, Leeds University, LS2 9JT, UK
² Biology Department, University of York, Heslington, York, YO10 5YW, UK

^* Authors for correspondence (e-mail: dc17{at}york.ac.uk; medjfxa{at}leeds.ac.uk)

Accepted 1 November 2006

Cip1-interacting zinc finger protein 1 (Ciz1) stimulates DNA replication in vitro and is required for mammalian cells to enter S phase. Here, we show that a significant proportion of Ciz1 is retained in nuclear foci following extraction with nuclease and high salt. This suggests that Ciz1 is normally immobilized by interaction with non-chromatin nuclear structures, consistent with the nuclear matrix. Furthermore, matrix-associated Ciz1 foci strikingly colocalize with sites of newly synthesized DNA in S phase nuclei, suggesting that Ciz1 is present in DNA replication factories. Analysis of green fluorescent protein-tagged fragments indicates that nuclear immobilization of Ciz1 is mediated by sequences in its C-terminal third, encoded within amino acids 708-830. Immobilization occurs in a cell-cycle-dependent manner, most probably during late G1 or early S phase, to coincide with its reported point of action. Although C-terminal domains are sufficient for immobilization, N-terminal domains are also required to specify focal organization. Combined with previous work, which showed that the DNA replication activity of Ciz1 is encoded by N-terminal sequences, we suggest that Ciz1 is composed of two functionally distinct domains: an N-terminal replication domain and a C-terminal nuclear matrix anchor. This could contribute to the formation or function of DNA replication factories in mammalian cells.

Key words: DNA replication, Cell cycle, Ciz1, Nuclear matrix