A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity

2008 ◽  
Vol 4 (6) ◽  
pp. 357-365 ◽  
Author(s):  
Alessia Montagnoli ◽  
Barbara Valsasina ◽  
Valter Croci ◽  
Maria Menichincheri ◽  
Sonia Rainoldi ◽  
...  
Keyword(s):  
Dna Replication ◽  
Antitumor Activity ◽  
Kinase Inhibitor ◽  
Cdc7 Kinase ◽  
Initiation Of Dna Replication

scholarly journals Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Chi-Chun Yang ◽  
Masahiro Suzuki ◽  
Shiori Yamakawa ◽  
Syuzi Uno ◽  
Ai Ishii ◽  
...  
Keyword(s):  
Dna Replication ◽  
Human Cells ◽  
Cdc7 Kinase ◽  
Initiation Of Dna Replication

scholarly journals Novel Fission Yeast Cdc7-Dbf4-Like Kinase Complex Required for the Initiation and Progression of Meiotic Second Division

2002 ◽  
Vol 22 (1) ◽  
pp. 309-320 ◽  
Author(s):  
Taro Nakamura ◽  
Michiko Nakamura-Kubo ◽  
Tomohiro Nakamura ◽  
Chikashi Shimoda
Keyword(s):  
Dna Replication ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Structural Features ◽  
Regulatory Subunit ◽  
Primary Role ◽  
Biological Functions ◽  
Cdc7 Kinase ◽  
Initiation Of Dna Replication ◽  
Novel Protein

ABSTRACT Cdc7, a conserved serine/threonine protein kinase, controls initiation of DNA replication. A regulatory subunit, Dbf4, stimulates the kinase activity of Cdc7 and recruits it to the replication origins. Schizosaccharomyces pombe has a homologous kinase complex, composed of Hsk1 and Dfp1/Him1. Here, we report a novel protein kinase of S. pombe, Spo4, which shares common structural features with the Cdc7 kinases. In spite of the structural similarities, Spo4 is dispensable for mitotic growth and premeiotic DNA replication. Intriguingly, spo4 null mutants are defective in initiation and progression of the second meiotic division. Spindles for meiosis II are often fragmented. Spo4 kinase activity is markedly enhanced when the enzyme is associated with its regulatory subunit, Spo6, a Dbf4-like protein. Expression of Spo4 is specifically induced during meiosis. Spo4 is preferentially present in nuclei, but this nuclear localization does not require Spo6. These results suggest that Spo4 is a Cdc7 kinase whose primary role is in meiosis, not in DNA replication. This is the first report of an organism which has two Cdc7-related kinase complexes with different biological functions.

A Novel Fluorescence-Based Screen for Inhibitors of the Initiation of DNA Replication in Bacteria

2019 ◽  
Vol 16 (3) ◽  
pp. 272-277 ◽  
Author(s):  
Rasmus N. Klitgaard ◽  
Anders Løbner-Olesen
Keyword(s):  
Dna Replication ◽  
High Throughput ◽  
Cyclic Peptide ◽  
Replication Initiation ◽  
False Positive Result ◽  
Over Expression ◽  
Initiator Protein ◽  
Dna Replication Initiation ◽  
Cellular Processes ◽  
Initiation Of Dna Replication

Background:One of many strategies to overcome antibiotic resistance is the discovery of compounds targeting cellular processes, which have not yet been exploited.Materials and Methods:Using various genetic tools, we constructed a novel high throughput, cellbased, fluorescence screen for inhibitors of chromosome replication initiation in bacteria.Results:The screen was validated by expression of an intra-cellular cyclic peptide interfering with the initiator protein DnaA and by over-expression of the negative initiation regulator SeqA. We also demonstrated that neither tetracycline nor ciprofloxacin triggers a false positive result. Finally, 400 extracts isolated mainly from filamentous actinomycetes were subjected to the screen.Conclusion:We concluded that the presented screen is applicable for identifying putative inhibitors of DNA replication initiation in a high throughput setup.

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