Academic literature on the topic 'Polo kinases/Cdc5'
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Journal articles on the topic "Polo kinases/Cdc5"
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Song, Sukgil, Tallessyn Z. Grenfell, Susan Garfield, Raymond L. Erikson, and Kyung S. Lee. "Essential Function of the Polo Box of Cdc5 in Subcellular Localization and Induction of Cytokinetic Structures." Molecular and Cellular Biology 20, no. 1 (January 1, 2000): 286–98. http://dx.doi.org/10.1128/mcb.20.1.286-298.2000.
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ABSTRACT Members of the polo subfamily of protein kinases play pivotal roles in cell proliferation. In addition to the kinase domain, polo kinases have a strikingly conserved sequence in the noncatalytic C-terminal domain, termed the polo box. Here we show that the budding-yeast polo kinase Cdc5, when fused to green fluorescent protein and expressed under its endogenous promoter, localizes at spindle poles and the mother bud neck. Overexpression of Cdc5 can induce a class of cells with abnormally elongated buds in a polo box- and kinase activity-dependent manner. In addition to localizing at the spindle poles and cytokinetic neck filaments, Cdc5 induces and localizes to additional septin ring structures within the elongated buds. Without impairing kinase activity, conservative mutations in the polo box abolish the ability of Cdc5 to functionally complement the defect associated with a cdc5-1 temperature-sensitive mutation, to localize to the spindle poles and cytokinetic neck filaments, and to induce elongated cells with ectopic septin ring structures. Consistent with the polo box-dependent subcellular localization, the C-terminal domain of Cdc5, but not its polo box mutant, is sufficient for subcellular localization, and its overexpression appears to inhibit cytokinesis. These data provide evidence that the polo box is required to direct Cdc5 to specific subcellular locations and induce or organize cytokinetic structures.
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Hardy, C. F., and A. Pautz. "A novel role for Cdc5p in DNA replication." Molecular and Cellular Biology 16, no. 12 (December 1996): 6775–82. http://dx.doi.org/10.1128/mcb.16.12.6775.
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DNA replication initiates from specific chromosomal sites called origins, and in the budding yeast Saccharomyces cerevisiae these sites are occupied by the origin recognition complex (ORC). Dbf4p is proposed to play a role in targeting the G1/S kinase Cdc7p to initiation complexes late in G1. We report that Dbf4p may also recruit Cdc5p to origin complexes. Cdc5p is a member of the Polo family of kinases that is required for the completion of mitosis. Cdc5p and Cdc7p each interact with a distinct domain of Dbf4p. cdc5-1 mutants have a plasmid maintenance defect that can be suppressed by the addition of multiple origins. cdc5-1 orc2-1 double mutants are synthetically lethal. Levels of Cdc5p were found to be cell cycle regulated and peaked in G2/M. These results suggest a role for Cdc5p and possibly Polo-like kinases at origin complexes.
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Park, Chong J., Jung-Eun Park, Tatiana S. Karpova, Nak-Kyun Soung, Li-Rong Yu, Sukgil Song, Kyung H. Lee, et al. "Requirement for the Budding Yeast Polo Kinase Cdc5 in Proper Microtubule Growth and Dynamics." Eukaryotic Cell 7, no. 3 (January 4, 2008): 444–53. http://dx.doi.org/10.1128/ec.00283-07.
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ABSTRACT In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of the budding yeast polo kinase Cdc5, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal noncatalytic polo box domain, a region that is critical for proper subcellular localization. One of these mutants, cdc5-11, exhibited a temperature-sensitive growth defect with an abnormal spindle morphology. Strikingly, provision of a moderate level of benomyl, a microtubule-depolymerizing drug, permitted cdc5-11 cells to grow significantly better than the isogenic CDC5 wild type in a FEAR (cdc Fourteen Early Anaphase Release)-independent manner. In addition, cdc5-11 required MAD2 for both cell growth and the benomyl-remedial phenotype. These results suggest that cdc5-11 is defective in proper spindle function. Consistent with this view, cdc5-11 exhibited abnormal spindle morphology, shorter spindle length, and delayed microtubule regrowth at the nonpermissive temperature. Overexpression of CDC5 moderately rescued the spc98-2 growth defect. Interestingly, both Cdc28 and Cdc5 were required for the proper modification of the spindle pole body components Nud1, Slk19, and Stu2 in vivo. They also phosphorylated these three proteins in vitro. Taken together, these observations suggest that concerted action of Cdc28 and Cdc5 on Nud1, Slk19, and Stu2 is important for proper spindle functions.
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Park, Chong Jin, Sukgil Song, Philip R. Lee, Wenying Shou, Raymond J. Deshaies, and Kyung S. Lee. "Loss of CDC5 Function in Saccharomyces cerevisiae Leads to Defects in Swe1p Regulation and Bfa1p/Bub2p-Independent Cytokinesis." Genetics 163, no. 1 (January 1, 2003): 21–33. http://dx.doi.org/10.1093/genetics/163.1.21.
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Abstract In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of budding yeast polo kinase Cdc5p, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal domain. Here we show that, at a semipermissive temperature, the cdc5-3 mutant exhibited a synergistic bud elongation and growth defect with loss of HSL1, a component important for normal G2/M transition. Loss of SWE1, which phosphorylates and inactivates the budding yeast Cdk1 homolog Cdc28p, suppressed the cdc5-3 hsl1Δ defect, suggesting that Cdc5p functions at a point upstream of Swe1p. In addition, the cdc5-4 and cdc5-7 mutants exhibited chained cell morphologies with shared cytoplasms between the connected cell bodies, indicating a cytokinetic defect. Close examination of these mutants revealed delayed septin assembly at the incipient bud site and loosely organized septin rings at the mother-bud neck. Components in the mitotic exit network (MEN) play important roles in normal cytokinesis. However, loss of BFA1 or BUB2, negative regulators of the MEN, failed to remedy the cytokinetic defect of these mutants, indicating that Cdc5p promotes cytokinesis independently of Bfa1p and Bub2p. Thus, Cdc5p contributes to the activation of the Swe1p-dependent Cdc28p/Clb pathway, normal septin function, and cytokinesis.
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Golsteyn, R. M., S. J. Schultz, J. Bartek, A. Ziemiecki, T. Ried, and E. A. Nigg. "Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5." Journal of Cell Science 107, no. 6 (June 1, 1994): 1509–17. http://dx.doi.org/10.1242/jcs.107.6.1509.
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polo and CDC5 are two genes required for passage through mitosis in Drosophila melanogaster and Saccharomyces cerevisiae, respectively. Both genes encode structurally related protein kinases that have been implicated in regulating the function of the mitotic spindle. Here, we report the characterization of a human protein kinase that displays extensive sequence similarity to Drosophila polo and S. cerevisiae Cdc5; we refer to this kinase as Plk1 (for polo-like kinase 1). The largest open reading frame of the Plk1 cDNA encodes a protein of 68,254 daltons, and a protein of this size is detected by immunoblotting of HeLa cell extracts with monoclonal antibodies raised against the C-terminal part of Plk1 expressed in Escherichia coli. Northern blot analysis of RNA isolated from human cells and mouse tissues shows that a single Plk1 mRNA of 2.3 kb is highly expressed in tissues with a high mitotic index, consistent with a possible function of Plk1 in cell proliferation. The Plk1 gene maps to position p12 on chromosome 16, a locus for which no associations with neoplastic malignancies are known. The Plk1 protein levels and its distribution change during the cell cycle, in a manner consistent with a role of Plk1 in mitosis. Thus, like Drosophila polo and S. cerevisiae Cdc5, human Plk1 is likely to function in cell cycle progression.
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Höfken, Thomas, and Elmar Schiebel. "Novel regulation of mitotic exit by the Cdc42 effectors Gic1 and Gic2." Journal of Cell Biology 164, no. 2 (January 19, 2004): 219–31. http://dx.doi.org/10.1083/jcb.200309080.
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The guanine nucleotide exchange factor Cdc24, the GTPase Cdc42, and the Cdc42 effectors Cla4 and Ste20, two p21-activated kinases, form a signal transduction cascade that promotes mitotic exit in yeast. We performed a genetic screen to identify components of this pathway. Two related bud cortex–associated Cdc42 effectors, Gic1 and Gic2, were obtained as factors that promoted mitotic exit independently of Ste20. The mitotic exit function of Gic1 was dependent on its activation by Cdc42 and on the release of Gic1 from the bud cortex. Gic proteins became essential for mitotic exit when activation of the mitotic exit network through Cdc5 polo kinase and the bud cortex protein Lte1 was impaired. The mitotic exit defect of cdc5-10 Δlte1 Δgic1 Δgic2 cells was rescued by inactivation of the inhibiting Bfa1-Bub2 GTPase-activating protein. Moreover, Gic1 bound directly to Bub2 and prevented binding of the GTPase Tem1 to Bub2. We propose that in anaphase the Cdc42-regulated Gic proteins trigger mitotic exit by interfering with Bfa1-Bub2 GTPase-activating protein function.
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Lee, K. S., and R. L. Erikson. "Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk activity induces multiple septation structures." Molecular and Cellular Biology 17, no. 6 (June 1997): 3408–17. http://dx.doi.org/10.1128/mcb.17.6.3408.
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Plk is a mammalian serine/threonine protein kinase whose activity peaks at the onset of M phase. It is closely related to other mammalian kinases, Snk, Fnk, and Prk, as well as to Xenopus laevis Plx1, Drosophila melanogaster polo, Schizosaccharomyces pombe Plo1, and Saccharomyces cerevisiae Cdc5. The M phase of the cell cycle is a highly coordinated process which insures the equipartition of genetic and cellular materials during cell division. To enable understanding of the function of Plk during M phase progression, various Plk mutants were generated and expressed in Sf9 cells and budding yeast. In vitro kinase assays with Plk immunoprecipitates prepared from Sf9 cells indicate that Glu206 and Thr210 play equally important roles for Plk activity and that replacement of Thr210 with a negatively charged residue elevates Plk specific activity. Ectopic expression of wild-type Plk (Plk WT) complements the cell division defect associated with the cdc5-1 mutation in S. cerevisiae. The degree of complementation correlates closely with the Plk activity measured in vitro, as it is enhanced by a mutationally activated Plk, T210D, but is not observed with the inactive forms K82M, D194N, and D194R. In a CDC5 wild-type background, expression of Plk WT or T210D, but not of inactive forms, induced a sharp accumulation of cells in G1. Consistent with elevated Plk activity, this phenomenon was enhanced by the C-terminally deleted forms WT deltaC and T210D deltaC. Expression of T210D also induced a class of cells with unusually elongated buds which developed multiple septal structures. This was not observed with the C-terminally deleted form T210D deltaC, however. It appears that the C terminus of Plk is not required for the observed cell cycle influence but may be important for polarized cell growth and septal structure formation.
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Park, Chong J., Sukgil Song, Thomas H. Giddings, Hyeon-Su Ro, Krisada Sakchaisri, Jung-Eun Park, Yeon-Sun Seong, Mark Winey, and Kyung S. Lee. "Requirement for Bbp1p in the Proper Mitotic Functions of Cdc5p in Saccharomyces cerevisiae." Molecular Biology of the Cell 15, no. 4 (April 2004): 1711–23. http://dx.doi.org/10.1091/mbc.e03-07-0461.
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The polo-box domain of the budding yeast polo kinase Cdc5p plays an essential role for targeting the catalytic activity of Cdc5p to spindle pole bodies (SPBs) and cytokinetic neck-filaments. Here, we report the isolation of Bbp1p as a polo-box interacting protein by a yeast two-hybrid screen. Bbp1p localizes to the periphery of the central plaque of the SPB and plays an important role in SPB duplication. Similarly, Cdc5p localized to the cytoplasmic periphery of the SPB. In vitro binding studies showed that Cdc5p interacted with the N-terminal domain of Bbp1p (Bbp1pΔC), but apparently not with Mps2p, a component shown to form a stable complex with Bbp1p. In addition, Bbp1p, but likely not Mps2p, was required for proper localization of Cdc5p to the SPB. The C-terminal coiled-coil domain of Bbp1p (Bbp1p243–385), which is crucial for both the homodimerization and the SPB localization, could target the localization-defective Cdc5pΔC to the SPB and induce the release of Cdc14p from the nucleolus. Consistent with this observation, expression of CDC5ΔC-BBP1243–385 under CDC5 promoter control partially complemented the cdc5Δ defect. These data suggest that Bbp1pΔC interacts with the polo-box domain of Cdc5p, and this interaction is critical for the subcellular localization and mitotic functions of Cdc5p.
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Park, Jung-Eun, Chong J. Park, Krisada Sakchaisri, Tatiana Karpova, Satoshi Asano, James McNally, Yangil Sunwoo, Sun-Hee Leem, and Kyung S. Lee. "Novel Functional Dissection of the Localization-Specific Roles of Budding Yeast Polo Kinase Cdc5p." Molecular and Cellular Biology 24, no. 22 (November 15, 2004): 9873–86. http://dx.doi.org/10.1128/mcb.24.22.9873-9886.2004.
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ABSTRACT Budding yeast polo kinase Cdc5p localizes to the spindle pole body (SPB) and to the bud-neck and plays multiple roles during M-phase progression. To dissect localization-specific mitotic functions of Cdc5p, we tethered a localization-defective N-terminal kinase domain of Cdc5p (Cdc5pΔC) to the SPB or to the bud-neck with components specifically localizing to one of these sites and characterized these mutants in a cdc5Δ background. Characterization of a viable, SPB-localizing, CDC5ΔC-CNM67 mutant revealed that it is defective in timely degradation of Swe1p, a negative regulator of Cdc28p. Loss of BFA1, a negative regulator of mitotic exit, rescued the lethality of a neck-localizing CDC5ΔC-CDC12 or CDC5ΔC-CDC3 mutant but yielded severe defects in cytokinesis. These data suggest that the SPB-associated Cdc5p activity is critical for both mitotic exit and cytokinesis, whereas the bud neck-localized Cdc5p is required for proper Swe1p regulation. Interestingly, a cdc5Δ bfa1Δ swe1Δ triple mutant is viable but grows slowly, whereas cdc5Δ cells bearing both CDC5ΔC-CNM67 and CDC5ΔC-CDC12 grow well with only a mild cell cycle delay. Thus, SPB- and the bud-neck-localized Cdc5p control most of the critical Cdc5p functions and downregulation of Bfa1p and Swe1p at the respective locations are two critical factors that require Cdc5p.
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Kumar, Praveen, and C. C. Wang. "Dissociation of Cytokinesis Initiation from Mitotic Control in a Eukaryote." Eukaryotic Cell 5, no. 1 (January 2006): 92–102. http://dx.doi.org/10.1128/ec.5.1.92-102.2006.
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ABSTRACTCytokinesis is initiated only after mitotic exit in eukaryotes. However, in the insect (procyclic) form of an ancient protist,Trypanosoma brucei, a blockade at the G2/M checkpoint results in an enrichment of anucleate cells (zoids), suggesting separated regulations between mitosis and cytokinesis (X. Tu and C. C. Wang, J. Biol. Chem.279:20519-20528, 2004). Polo-like kinases (Plks) are known to play critical roles in controlling both mitosis and cytokinesis. A singlePlkhomologue inT. brucei, TbPLK, was found to be capable of complementing the Plk (Cdc5) functions inSaccharomyces cerevisiae, thus raising the question of how it may function in the trypanosome with cytokinesis dissociated from mitosis. Depletion of TbPLK in the procyclic form ofT. bruceiby RNA interference resulted in growth arrest with accumulation of multiple nuclei, kinetoplasts, basal bodies, and flagella in approximately equal numbers among individual cells. There were, however, few zoids detectable, indicating inhibited cytokinesis with unblocked mitosis and kinetoplast segregation. TbPLK is thus apparently involved only in initiating cytokinesis inT. brucei. Overexpression of TbPLK in the trypanosome did not affect cell growth, but 13% of the resulting population was in the zoid form, suggesting runaway cytokinesis. An immunofluorescence assay indicated that TbPLK was localized in a chain of likely flagellum attachment zones in the cytoskeleton. In a dividing cell, a new line of such zones appeared closely paralleling the existing one, which could constitute the cleavage furrow. An exposed region of TbPLK at the anterior tip of the cell may provide the trigger of cytokinesis. Taken together, our results revealed a novel mechanism of cytokinesis initiation in the trypanosome that may serve as a useful model for further in-depth investigations.
Dissertations / Theses on the topic "Polo kinases/Cdc5"
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MONTANI, FRANCESCA. "MOLECULAR MECHANISMS UNDERLYING CDC14 ACTIVATION DURING MITOTIC EXIT IN SACCHAROMYCES CEREVISIAE." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/214785.
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In budding yeast, progression through anaphase and exit from mitosis are controlled by the conserved protein phosphatase Cdc14. The activity of Cdc14 is regulated in space and time by changes in its subcellular localization. For most of the cell cycle up to metaphase, the phosphatase is sequestered in the nucleolus, by binding to a competitive inhibitor called Cfi1 (also known as Net1) (Shou et al., 1999; Straight et al., 1999; Visintin et al., 1999). During anaphase, Cdc14 is released from its inhibitor by the sequential activation of two signaling cascades, the Cdc Fourteen Early Anaphase Release (FEAR) network and the Mitotic Exit Network (MEN). Once released Cdc14 spreads throughout the nucleus and the cytoplasm, where it reaches its targets and promotes progression through and exit from mitosis (Pereira et al., 2002; Shou et al., 1999; Stegmeier et al., 2002; Visintin et al., 1999; Yoshida et al., 2002). Several in vivo and in vitro observations suggest that phosphorylation of Cdc14 and/or Cfi1 is responsible for the dissociation of Cdc14 from its inhibitor. Three kinases have been implicated in the process: the polo-like kinase Cdc5, the Clb2-Cdk complex and the MEN kinase Dbf2 (Azzam et al., 2004; Geymonat et al., 2003; Hu and Elledge, 2002; Hu et al., 2001; Mohl et al., 2009; Pereira et al., 2002; Queralt et al., 2006; Stegmeier et al., 2002; Visintin et al., 2003; Yoshida and Toh-e, 2002).
The aim of my project was to assess the contribution of the above-mentioned kinases and to identify the molecular mechanisms by which these kinases mediate the release of Cdc14 from its inhibitor. By modulating the kinases of interest alone or in mutual combination we found that Cdc14 is released from the nucleolus by the combined activity of two kinases, Cdc5 always and either Clb-Cdks or Dbf2. Once active, Cdc14 triggers a negative feedback loop that, in the presence of stable levels of mitotic cyclins, generates periodic cycles of Cdc14 release and sequestration. Similar phenotypes have been described for yeast bud formation and centrosome duplication. A common theme emerges where events that must happen only once per cycle, although intrinsically capable of oscillations, are limited to one occurrence by their coupling with the cyclin-Cdk cell cycle engine.
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Rawal, C. "ROLE OF POLO KINASE CDC5 AND SLX4-RTT107 COMPLEX IN CHECKPOINT SIGNALING DURING DNA DAMAGE IN S. CEREVISIAE." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/335192.
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The integrity of genomic DNA is continuously jeopardized through of environmental stresses such as UV light, ionizing radiations and various chemicals in addition to cellular byproducts such as reactive oxygen species. Furthermore, structural or chemical hindrances also affect the basic cellular processes (replication, transcription and translation) compromising genome stability. All the eukaryotic cells have thus evolved mechanisms to detect such genomic lesions and activate a surveillance mechanisms termed as checkpoint activation to arrest cell cycle, which in term provide time to repair the lesion using a suitable pathway to maintain genome stability. The resumption of cell cycle after the repair is also an important and finely regulated mechanisms. Indeed, resumption of cell cycle in case of faulty/un-repaired damage compromises genome integrity and may lead to cancer.
In this thesis, I studied the role of Polo-kinase Cdc5 and DNA repair scaffold complex-Slx-Rtt107, specifically in response to one of the most deleterious lesion, DNA double strand break (DSB) in budding yeast Saccharomyces cerevisiae. The human counterpart Polo-like kinase 1 is overexpressed in many cancers, while Slx4/FANCP is one of the proteins involved in Fanconi anemia repair pathway.
In first part, we characterized the role of phosphorylation of Threonine 238 in the activation loop of the Cdc5 kinase domain in unperturbed cell cycle and in response to repairable and unrepairable DSB. Using alanine/ aspartic acid mutagenesis and genetic approaches we delineated the requirement of T238 phosphorylation of Cdc5. Interestingly, we discovered that absence of T238 phosphorylation of Cdc5, even though doesn’t affect the normal cell cycle, affects kinase activity and leads to defect in checkpoint adaptation and recovery after one DSB. Importantly, we also found that cdc5-T238A cells also have altered genome stability, assessed by using multiple genetic approaches.
In second part, we characterized the role of Slx4-Rtt107 complex in modulating the level of checkpoint signalling and initial processing of DSB. Indeed in the absence of functional Slx4-Rtt107 complex, we found slower processing of DSB and hyper-activated checkpoint signalling which is due to increased binding of checkpoint adaptor protein Rad9 at the lesion. Importantly, this hyper-activated checkpoint has consequent effect on cell cycle resumption and proliferation in response to various DNA damaging agents.
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Neutzner, Melanie. "Regulatoren des Zellteilungszyklus der Hefe Saccharomyces cerevisiae : die Polo-Kinase Cdc5 und der Ubiquitinierungsfaktor Hct1 /." [S.l. : s.n.], 2003. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10605153.
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CLAUDI, CECILIA. "POLO-LIKE KINASE CDC5 CONTRIBUTES TO MITOTIC SPINDLE ELONGATION VIA THE KINESIN-5 MOTOR PROTEIN CIN8." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/607694.
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Proper chromosome segregation requires an orderly sequence of events, whereby spindle elongation follows the dissolution of sister chromatid linkages. Chromosome segregation starts at the onset of anaphase when the separase triggers the cleavage of cohesin, a protein complex that holds sister chromatids together. Next, chromatids are segregated into the daughter cells by the pulling force of the mitotic spindle. The mitotic spindle is a sophisticated and complex machinery built of microtubules, microtubule associated proteins and motor proteins. Despite the fundamental role of the mitotic spindle, the molecular mechanisms underlying its regulation remain elusive. Proper spindle function requires that microtubule dynamics are stabilized at anaphase. This change in microtubule dynamics is perceived as dictated by a shift in the balance of kinase and phosphatase activities in favor of the phosphatases. The finding that cells simultaneously lacking the polo-like kinase Cdc5 and the phosphatase Cdc14 cannot progress through anaphase albeit having cleaved cohesin due to defects in spindle elongation, challenges the view of mitotic exit as a time for protein dephosphorylation.
The aim of my work is to understand the molecular mechanism by which the two proteins contribute to anaphase spindle elongation, with a particular focus on the role of Cdc5. We identified the kinesin 5 motor protein Cin8 as a key target of the “Cdc14-Cdc5” spindle elongation pathway. We show that besides being dephosphorylated by Cdc14, Cin8 is also phosphorylated by Cdc5 on residues S409 and S441, and that this phosphorylation is crucial for the function of the kinesin in anaphase spindle elongation, likely because of the impact it has on the interaction between Cin8 and microtubules. Since these residues, S409 and S441, are located within a highly conserved stretch of amino acids, it will be interesting to test whether this regulation is conserved in other vertebrates as well. The finding that Cin8 is simultaneously a substrate of a kinase and a phosphatase sheds light on the complexity of mitotic exit regulation and is in complete agreement with recent data showing that approximately equal numbers of phosphosites are phosphorylated and dephosphorylated during mitotic progression and exit. Since it appears that phosphorylation and dephosphorylation events are equally important to the point that kinases and phosphatases cooperate to regulate the same substrates, the view of mitotic exit as the realm of phosphatases is dismantled and the continuous need for single molecule studies in addition to global analyses investigation is put forward.
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Vidanes, Genevieve M. "Suppression of the DNA damage checkpoint by the Saccharomyces cerevisiae polo-like kinase, CDC5, to promote adaptation." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3352477.
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MASSARI, LUCIA FRANCESCA. "Complete resolution of sister chromatid intertwines requires the Polo-like kinase Cdc5 and the phosphatase Cdc14 in budding yeast." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/556680.
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During mitosis the newly replicated genetic material, organized in sister chromatids, is equally subdivided into the daughter cells through a fine-regulated process called chromosome segregation. Sister chromatids are held together and identified as sisters by cohesin. At the metaphase-to-anaphase transition, when all chromatids are correctly attached to the spindle, cohesin is cleaved and chromosome segregation initiates. Beside cohesin, all linkages between sister chromatids need to be removed to allow for their complete separation. Additional linkages include DNA linkages (or sister chromatid intertwines, SCIs), such as recombination intermediates and DNA catenanes.
In Saccharomyces cerevisiae a mutant that lacks the activities of the Polo-like kinase Cdc5 and the phosphatase Cdc14, two major mitotic regulators, has been identified that proved to be particularly suitable for studying SCIs that persist in mitosis. The cdc5 cdc14 double mutant arrests with short and stable mitotic spindles and unseparated nuclei, despite having cleaved cohesin. In addition to having a spindle elongation defect, these cells are also impaired in the resolution of cohesin-independent linkages between chromatids.
We found that these linkages mostly consist of DNA catenanes, that persist in cdc5 cdc14 cells at their terminal arrest and that are sufficient to counteract spindle elongation. Our results suggest that Cdc5 is required for their resolution.
This finding, together with the knowledge that Cdc5 promotes Cdc14 activation and that both proteins are essential for spindle elongation and mitotic exit, allows us to speculate that they coordinate different aspects of chromosome segregation to guarantee genome integrity throughout mitosis.
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Argunhan, Bilge. "Interplay between Dbf4-dependent Cdc7 kinase and polo-like kinase unshackles mitotic recombination mechanisms by promoting synaptonemal complex disassembly." Thesis, University of Sussex, 2016. http://sro.sussex.ac.uk/id/eprint/59019/.
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Meiotic recombination is initiated by self-inflicted DNA breaks and primarily involves homologous chromosomes, whereas mitotic recombination involves sister chromatids. Whilst the mitotic recombinase Rad51 exists during meiosis, its activity is suppressed in favour of the meiosis-specific recombinase, Dmc1, thus establishing a meiosis-specific mode of homologous recombination (HR). A key contributor to the suppression of Rad51 activity is the synaptonemal complex (SC), a meiosis-specific chromosomal structure that adheres homologous chromosomes along their entire lengths. Here, in budding yeast, we show that two major cell cycle kinases, Dbf4-dependent Cdc7 kinase (DDK) and Polo-kinase (Cdc5), collaborate to link the mode change of HR to the meiotic cell cycle by. This regulation of HR is through the SC. During prophase I, DDK is shown to maintain SC integrity and thus inhibition of Rad51. Cdc5, which is produced during the prophase I/metaphase I transition, interacts with DDK to cooperatively destroy the SC and remove Rad51 inhibition. By enhancing the interaction between DDK and Cdc5 or depleting DDK at late prophase I, meiotic DNA breaks are repaired even in the absence of Dmc1 by utilising Rad51. We propose that the interplay between DDK and Polo-kinase reactivates mitotic HR mechanisms to ensure complete repair of DNA breaks before meiotic chromosomem segregation.
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Arnold, Lea [Verfasser], and Wolfgang [Akademischer Betreuer] Seufert. "Studien zur Regulation und Funktion der Polo-Kinase Cdc5 im Zellteilungszyklus der Hefe Saccharomyces cerevisiae / Lea Arnold. Betreuer: Wolfgang Seufert." Regensburg : Universitätsbibliothek Regensburg, 2013. http://d-nb.info/1047236869/34.
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FINARDI, ALICE. "THE POLO-LIKE KINASE CDC5 AND THE CDK-COUNTERACTING PHOSPHATASE CDC14 PLAY DISTINCT ROLES IN THE RESOLUTION OF DNA LINKAGES IN MITOSIS." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/906786.
Full textAbstract:
During mitosis, the newly duplicated genetic material, organized in pairs of sister chromatids, is distributed between the daughter cells by the spindle machinery, in a process called chromosome segregation. Errors in this process can compromise genome integrity. Faithful chromosome segregation requires the removal of all sorts of cohesion between sister chromatids. Although the main contributors of sister chromatid cohesion are cohesin complexes, which are cleaved at anaphase onset, another source of cohesion is represented by DNA linkages, also called Sister Chromatid Intertwines (SCIs). These linkages comprise unreplicated segments, recombination intermediates, and double-stranded catenanes. If not properly removed, SCIs can break during cell division causing DNA damage and jeopardizing genome stability. Although most DNA linkages are removed before mitosis, their complete resolution only occurs concomitantly with chromosome segregation, in a process whose regulation is still poorly understood.
In this thesis, to investigate the mechanisms of SCI resolution during mitosis, we exploited the unique phenotype of S. cerevisiae cells lacking the activities of the polo-like kinase Cdc5 and the Cdk-counteracting phosphatase Cdc14. These cells arrest after cohesin cleavage, with short bipolar spindles and undivided nuclei, because impaired in spindle elongation. Evidence suggests that cdc5 cdc14 cells are also impaired in sister chromatid separation, due to the presence of unresolved SCIs, and previous work in our laboratory revealed that these linkages mainly consist of DNA catenanes. Here, we found that both Cdc14 and Cdc5 contribute to the resolution of DNA linkages, with different functions. Cdc14 is mainly involved in nucleolar segregation and processing of recombination intermediates, while Cdc5 seems to act through a more generalized mechanism and promote the removal of DNA catenanes. At the molecular level, Cdc14 acts through its known substrate Yen1. On the other hand, we found that Cdc5 controls post-translational modification of the decatenating enzyme Top2 during mitosis, particularly conjugation with small ubiquitin-like modifier (SUMO) and, possibly, also phosphorylation. The polo-like kinase is known to inactivate the SUMO protease Ulp2 in metaphase, thus increasing SUMOylation of Ulp2 substrates, like Top2. Since the decatenation defect of cdc5 cells correlates with a dysregulation of the SUMO pathway and this pathway is known to regulate sister chromatid cohesion, we speculate that the hyperactivation of Ulp2 may be the reason behind the sister chromatid separation defect of cdc5 cells. Taken together, our findings integrate the current knowledge of the mechanisms of sister chromatid separation and allow us to propose a model that foresees Cdc5 and Cdc14 coordinating cohesin cleavage and spindle elongation with the removal of DNA intertwines.
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Donnianni, R. A. "Elevated levels of the polo kinase Cdc5 overridethe Mec1/ATR checkpoint in budding yeast by acting at different steps of the signaling pathway." Doctoral thesis, Università degli Studi di Milano, 2009. http://hdl.handle.net/2434/158403.
Full textAbstract:
Checkpoints are surveillance mechanisms that constitute a barrier to oncogenesis by preserving genome integrity. Loss of
checkpoint function is an early event in tumorigenesis. Polo kinases (Plks) are fundamental regulators of cell cycle
progression in all eukaryotes and are frequently overexpressed in tumors. Through their polo box domain, Plks target
multiple substrates previously phosphorylated by CDKs and MAPKs. In response to DNA damage, Plks are temporally
inhibited in order to maintain the checkpoint-dependent cell cycle block while their activity is required to silence the
checkpoint response and resume cell cycle progression. Here, we report that, in budding yeast, overproduction of the Cdc5
polo kinase overrides the checkpoint signaling induced by double strand DNA breaks (DSBs), preventing the
phosphorylation of several Mec1/ATR targets, including Ddc2/ATRIP, the checkpoint mediator Rad9, and the transducer
kinase Rad53/CHK2. We also show that high levels of Cdc5 slow down DSB processing in a Rad9-dependent manner, but do
not prevent the binding of checkpoint factors to a single DSB. Finally, we provide evidence that Sae2, the functional
ortholog of human CtIP, which regulates DSB processing and inhibits checkpoint signaling, is regulated by Cdc5. We
propose that Cdc5 interferes with the checkpoint response to DSBs acting at multiple levels in the signal transduction
pathway and at an early step required to resect DSB ends.
Conference papers on the topic "Polo kinases/Cdc5"
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Апарцин, Константин, and Konstantin Apartsin. "The results of fundamental and translational research carried out In the Department of Biomedical Research and Technology of the SBRAS INC in 2012-2016." In Topical issues of translational medicine: a collection of articles dedicated to the 5th anniversary of the day The creation of a department for biomedical research and technology of the Irkutsk Scientific Center Siberian Branch of RAS. Москва: INFRA-M Academic Publishing LLC., 2017. http://dx.doi.org/10.12737/conferencearticle_58be81eca22ad.
Full textAbstract:
The results of basic and translational research of the Department of Biomedical Research and Technology of Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences in 2012–2016 The paper presents the results of interdisciplinary research carried out in 2012–2016. The review includes the study of molecular mechanisms of pathogenesis of reparative regeneration, experimental substantiation of methods of diagnosis and prognosis of systemic disturbances of regeneration process, carrying out clinical trials of medicinal products and the formation of observational studies in the field of personalized medicine, the preparation of practical recommendations on the testing of previously developed surgical methods of prevention or correction of postoperative recovery disorders. New data are obtained on the role of the MAP-kinase cascade in the process of regeneration of muscle tissue. It has been established, that with a significant increase of VEGF concentration at the site of the repair of ischemic myocardium, progenitor cells with the CD34+CD45+ phenotype appear, which opens up prospects for the development of biotechnology to restore the damaged myocardium with its own pool of progenitor cells. The new data on the role of growth factors in the post-infarction remodeling are found. It has been revealed, that in local increase of selenium concentration low intensity of mineralization of forming callus in the area of the damage is observed and the formation of bone regeneration slows down. Prospects for the use of nanocomposites of elemental selenium for modulation of reparative response are marked. The dynamics of the level of free circulating mitochondrial DNA (mtDNA) of blood in the early stages of experimental dyslipidemia has been studied. Atherogenic blood factors do not have a significant effect on the release of the mtDNA from dyslipidemia target cells. On the model of acute small-focal myocardial ischemia, we revealed the increase in the mtDNA levels. Prospects of broadcast of diagnostic mtDNA monitoring technology in myocardial ischemia have been marked. The mtDNA monitoring was first tested as a molecular risk pattern in acute coronary syndrome. In survived patients, the concentration of freely circulating mtDNA in blood plasma was 164 times lower. The probability of death of the patient with a high level of mtDNA (over 4000 copies/mL) was 50 % (logit analysis). Methodological level of translational research in the ISC SB RAS has increased due to effective participation in international multi-center clinical trials of drugs, mainly direct anticoagulants: fondaparinux, edoksabana, betriksabana. “Feedback broadcast” of the results of clinical trials of p38-kinase inhibitor, was carried out in the process of changing the model (initially – neuropathic pain) for coronary atherosclerosis. Technologies of pharmacogenetic testing and personalized treatment of diseases in the employees of the Irkutsk Scientific Center were applied. Step T2. Previously developed at the Irkutsk State Medical University and the Irkutsk Scientific Center of Surgery and Traumatologies approaches to surgical prevention and medicinal correction of postoperative hyposplenism were translated into practical health care. Thus, these results obtained in different areas of translational medicine will determine scientific topics of the department in future research cycle.