Schizosaccharomyces pombe replication protein Cdc45/Sna41 requires Hsk1/Cdc7 and Rad4/Cut5 for chromatin binding

Dolan, William P.; Sherman, Daniel; Forsburg, Susan L.

doi:10.1007/s00412-004-0302-8

Cited by 25 publications

(23 citation statements)

References 65 publications

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“…In budding yeast the Rad4 TopBP1 homologue Dpb11 has been shown to interact with both Sld2 and Sld3 and those events have been shown to be CDK-dependent and similar data have recently been reported in metazoans (6,7,8,10,11,12,49). Chromatin association of Cdc45 has been previously shown to be dependent upon Mcm10, Rad4 TopBP1 , Sld3 and the GINS complex (22,23,24,47). The data presented in Supplementary Fig.…”

Section: ) Predictably Mcm4supporting

confidence: 75%

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Mcm10 interacts with Rad4/Cut5TopBP1 and its association with origins of DNA replication is dependent on Rad4/Cut5TopBP1

et al. 2011

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2Running title: Rad4 TopPB1 interacts with Mcm10 and associates with stalled replication forks. and Sld3 and to be required for the stable origin association of these two proteins. Rad4 TopBP1 chromatin association at stalled replication forks was found to be dependent upon the checkpoint protein Rad9, which was not required for Rad4 TopBP1 origin association. Comparison of the levels of chromatin association at origins of replication and stalled replication forks and the differential requirement for Rad9 suggest functional differences for Rad4 TopBP1 at these distinct sites.4

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Section: ) Predictably Mcm4supporting

confidence: 75%

“…Chromatin association of Cdc45 has been shown to be dependent upon Mcm10, DDK activity and Rad4/Cut5 TopBP1 (hereafter Rad4 TopBP1 ) function (22,23). DNA replication origin association of Rad4 TopBP1 and Cdc45 were found to be GINS dependent in contrast to Sld3 loading (24).…”

Section: Introductionmentioning

confidence: 99%

Mcm10 interacts with Rad4/Cut5TopBP1 and its association with origins of DNA replication is dependent on Rad4/Cut5TopBP1

et al. 2011

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“…The dependence on the damage checkpoint is not seen in mutations that affect replication initiation only; orp1-4, a mutant defective for prereplicative complex formation and replication initiation (Grallert and Nurse 1996;Dolan et al 2004), is viable in combination with Drad17 and Drad1 ( Table 1). The dependency of hsk1 cells on an intact damage checkpoint suggests that the hsk1-1312 itself generates DNA damage.…”

Section: Resultsmentioning

confidence: 99%

“…In experiments with temperaturesensitive strains, cultures were grown at 25°and shifted to 36°for 4 hr (approximately one cell cycle). Arrests of temperature-sensitive strains confirmed by flow cytometry were performed as described (Dolan et al 2004; data not shown). Synthetic lethal mutants were those unable to generate a viable double mutant compared to formation of .20 nonparental wild-type colonies from the same cross.…”

Section: Methodsmentioning

confidence: 99%

“…These images were viewed and contrast adjusted in Canvas 8-10 (ACD Systems, Victoria, BC, Canada). For two experiments, 100-500 cells were counted per experiment.In situ chromatin binding assays: Assays were modified from (Dolan et al 2004) as follows: hsk1HA, dfp1HA, and dfp1-(1-459)HA strains were viewed with a 1:250 dilution of monoclonal anti-HA 16B12 (BabCO, Berkeley, CA). dfp1v5 strains were immunostained with a 1:500 dilution of mouse anti-v5 antibody (Invitrogen, Carlsbad, CA).…”

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Fission Yeast Hsk1 (Cdc7) Kinase Is Required After Replication Initiation for Induced Mutagenesis and Proper Response to DNA Alkylation Damage

Dolan

Schmidt

et al. 2010

Genetics

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Genome stability in fission yeast requires the conserved S-phase kinase Hsk1 (Cdc7) and its partner Dfp1 (Dbf4). In addition to their established function in the initiation of DNA replication, we show that these proteins are important in maintaining genome integrity later in S phase and G2. hsk1 cells suffer increased rates of mitotic recombination and require recombination proteins for survival. Both hsk1 and dfp1 mutants are acutely sensitive to alkylation damage yet defective in induced mutagenesis. Hsk1 and Dfp1 are associated with the chromatin even after S phase, and normal response to MMS damage correlates with the maintenance of intact Dfp1 on chromatin. A screen for MMS-sensitive mutants identified a novel truncation allele, rad35 (dfp1-(1-519)), as well as alleles of other damage-associated genes. Although Hsk1-Dfp1 functions with the Swi1-Swi3 fork protection complex, it also acts independently of the FPC to promote DNA repair. We conclude that Hsk1-Dfp1 kinase functions post-initiation to maintain replication fork stability, an activity potentially mediated by the C terminus of Dfp1.T HE Hsk1 protein kinase, the fission yeast ortholog of Saccharomyces cerevisiae Cdc7, is a conserved protein essential for the initiation of DNA replication (Masai et al. 1995;Brown and Kelly 1998;Snaith et al. 2000). Data from many systems suggest that the kinase functions at individual replication origins to activate the prereplication complex (preRC) through phosphorylation of the MCM helicase and other subunits (reviewed in Forsburg 2004). In fission yeast, Hsk1 kinase activity is limited to S phase by its regulatory subunit Dfp1, which is transcriptionally and posttranslationally regulated to restrict its peak of activity to S phase (Brown and Kelly 1999;Takeda et al. 1999). The requirement for Dfp1 (in S. cerevisiae, Dbf4) is similar to the dependence of CDK kinases on cyclin activity; thus, the Ccd7 kinase family has been dubbed DDK (Dbf4-dependent kinases) ( Johnston et al. 1999;Duncker and Brown 2003). Hsk1 is a target of the Cds1 checkpoint kinase and undergoes Cds1-dependent phosphorylation during hydroxyurea (HU) treatment in vivo and in vitro (Snaith et al. 2000). Interestingly, deletion of Dcds1 partly rescues hsk1-1312 temperature sensitivity, which suggests that Hsk1 is negatively regulated by the replication checkpoint. In turn, Cds1 is poorly activated in hsk1 mutants after HU treatment, indicating that there may be a feedback loop linking these two kinases (Snaith et al. 2000;Takeda et al. 2001). hsk1 mutants are sensitive to HU treatment, with a phenotype suggesting a specific defect in recovery (Snaith et al. 2000).DDK kinases have substrates outside of the replication initiation pathway. Functional dissection of Schizosaccaromyces pombe Dfp1 identifies separate regions that are required for checkpoint response (N-terminal domain; Takeda et al. 1999;Fung et al. 2002), for centromere cohesion and replication (MIR domain;Bailis et al. 2003;Hayashi et al. 2009) and for proper response to alkylat...

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Novel protein contact points among TP53 and minichromosome maintenance complex proteins 2, 3, and 5

et al. 2022

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Objective Identify protein contact points between TP53 and minichromosome maintenance (MCM) complex proteins 2, 3, and 5 with high resolution allowing for potential novel Cancer drug design. Methods A next‐generation sequencing‐based protein–protein interaction method developed in our laboratory called AVA‐Seq was applied to a gold‐standard human protein interaction set. Proteins including TP53, MCM2, MCM3, MCM5, HSP90AA1, PCNA, NOD1, and others were sheared and ligated into the AVA‐Seq system. Protein–protein interactions were then identified in both mild and stringent selective conditions. Results Known interactions among MCM2, MCM3, and MCM5 were identified with the AVA‐Seq system. The interacting regions detected between these three proteins overlap with the structural data of the MCM complex, and novel domains were identified with high resolution determined by multiple overlapping fragments. Fragments of wild type TP53 were shown to interact with MCM2, MCM3, and MCM5, and details on the location of the interactions were provided. Finally, a mini‐network of known and novel cancer protein interactions was provided, which could have implications for fundamental changes in multiple cancers. Conclusion We provide a high‐resolution mini‐interactome that could direct novel drug targets and implicate possible effects of specific cancer mutations.

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Schizosaccharomyces pombe replication protein Cdc45/Sna41 requires Hsk1/Cdc7 and Rad4/Cut5 for chromatin binding

Cited by 25 publications

References 65 publications

Mcm10 interacts with Rad4/Cut5TopBP1 and its association with origins of DNA replication is dependent on Rad4/Cut5TopBP1

Mcm10 interacts with Rad4/Cut5TopBP1 and its association with origins of DNA replication is dependent on Rad4/Cut5TopBP1

Fission Yeast Hsk1 (Cdc7) Kinase Is Required After Replication Initiation for Induced Mutagenesis and Proper Response to DNA Alkylation Damage

Novel protein contact points among TP53 and minichromosome maintenance complex proteins 2, 3, and 5

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