Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA replication in mammalian cells occurs in discrete nuclear foci. Here we show that terminally differentiated myotubes can be induced to reenter S phase and show the same pattern of replication foci as cycling cells. We used this cellular system to analyze the interaction of cell cycle proteins with these foci in vivo. Cyclin A and cdk2, but not cyclin B1 and cdc2, were specifically localized at nuclear replication foci, just like the replication protein proliferating cell nuclear antigen. A potential target of cyclin A and cdk2 is the 34 kd subunit of replication protein A (RPA34). In contrast with the 70 kd subunit, which localizes to the foci, RPA34 was not detected at these replication sites, which may reflect a transient interaction. The specific localization of cyclin A and cdk2 at nuclear replication foci provides a direct link between cell cycle regulation and DNA replication.
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PMID:Reversal of terminal differentiation and control of DNA replication: cyclin A and Cdk2 specifically localize at subnuclear sites of DNA replication. 840 87

Using alternative reading frames, the human ARF-INK4a locus encodes two unrelated proteins that both function in tumor suppression. p16(INK4a) maintains the retinoblastoma protein in its growth-suppressive state through inhibition of cyclin D-dependent kinase activity, whereas ARF binds with MDM2 and stabilizes p53. The majority of the activity of ARF to date is ascribed to its ability to activate p53, resulting in a G(1) cell cycle arrest or apoptosis. We show here that ARF colocalizes with DNA replication protein A (RPA32) and that overexpression of ARF reduces the rate of DNA synthesis resulting in accumulation of an S-phase cell population. Impediment of DNA synthesis by ARF can occur and becomes more evident in the absence of p53. Hence, the biological consequence of ARF induction varies dependent on cellular p53 status, inducing predominantly a G(1) arrest or apoptosis in p53-positive cells or causing S-phase retardation when p53 function is comprised.
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PMID:Human tumor suppressor ARF impedes S-phase progression independent of p53. 1186

Replication protein A (RPA) is a three subunit single-stranded DNA-binding protein required for DNA replication. In Xenopus, RPA assembles in nuclear foci that form before DNA synthesis, but their significance in the assembly of replication initiation complexes has been questioned. Here we show that the RPA34 regulatory subunit is dephosphorylated at the exit of mitosis and binds to chromatin at detergent-resistant replication foci that co-localize with the catalytic RPA70 subunit, at both the initiation and elongation stages of DNA replication. By contrast, the RPA34 phosphorylated form present at mitosis is not chromatin bound. We further demonstrate that RPA foci assemble on chromatin before initiation of DNA replication at sites functionally defined as initiation replication sites. Association of RPA with these sites does not require nuclear membrane formation, and is sensitive to the S-CDK inhibitor p21. We also provide evidence that RPA34 is present at initiation complexes formed in the absence of MCM3, but which contain MCM4. In such conditions, replication foci can form, and short RNA-primed nascent DNAs of discrete size are synthesized. These data show that in Xenopus, the hypophosphorylated form of RPA34 is a component of the pre-initiation complex.
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PMID:A hypophosphorylated form of RPA34 is a specific component of pre-replication centers. 1545 45