Ciz1 promotes mammalian DNA replication

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Ciz1 promotes mammalian DNA replication.

Using a cell-free system that reconstitutes initiation of mammalian DNA replication, we identified a cyclin A-responsive protein, p21(Cip1)-interacting zinc finger protein 1 (Ciz1). In cell-free experiments, Ciz1 protein increases the number of nuclei that initiate DNA replication, and in intact cells GFP-tagged Ciz1 stimulates DNA synthesis, in both a wild-type and a p21(Cip1) null background....

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Ciz1 cooperates with cyclin-A-CDK2 to activate mammalian DNA replication in vitro.

Initiation of mammalian DNA replication can be reconstituted from isolated G1-phase nuclei and cell extracts, supplemented with cyclin-dependent protein kinases (CDKs). Under these conditions, cyclin E supports pre-replication complex assembly, whereas cyclin-A-associated kinase acts later to terminate assembly and activate DNA replication. The mechanism by which these events are coordinated is...

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Cyclin-A-CDK2-mediated phosphorylation of CIZ1 blocks replisome formation and initiation of mammalian DNA replication.

CIZ1 is a nuclear matrix protein that cooperates with cyclin A2 (encoded by CCNA2) and CDK2 to promote mammalian DNA replication. We show here that cyclin-A-CDK2 also negatively regulates CIZ1 activity by phosphorylation at threonines 144, 192 and 293. Phosphomimetic mutants do not promote DNA replication in cell-free and cell-based assays, and also have a dominant-negative effect on replisome ...

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The Role of Cdkn1A-Interacting Zinc Finger Protein 1 (CIZ1) in DNA Replication and Pathophysiology

Cdkn1A-interacting zinc finger protein 1 (CIZ1) was first identified in a yeast-2-hybrid system searching for interacting proteins of CDK2 inhibitor p21(Cip1/Waf1). Ciz1 also binds to CDK2, cyclin A, cyclin E, CDC6, PCNA, TCF4 and estrogen receptor-α. Recent studies reveal numerous biological functions of CIZ1 in DNA replication, cell proliferation, and differentiation. In addition, splicing va...

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

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 m...

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ژورنال

عنوان ژورنال: Journal of Cell Science

سال: 2005

ISSN: 1477-9137,0021-9533

DOI: 10.1242/jcs.01599