The S. pombe CDK5 Orthologue Pef1 Cooperates with Three Cyclins, Clg1, Pas1 and Psl1, to Promote Pre-Meiotic DNA Replication

Meiosis is a specialized cell division process that mediates genetic information transfer to the next generation. Meiotic chromosomal segregation occurs when DNA replication is completed during the pre-meiotic S phase. Here, we show that Schizosaccharomyces pombe Pef1, an orthologue of mammalian cyclin-dependent kinase 5 (CDK5), is required to promote pre-meiotic DNA replication. We examined the efficiency of meiotic initiation using pat1-114 mutants and found that, meiotic nuclear divisions did not occur in the pef1Δ pat1-114 strain. Deletion of pef1 also suppressed the expression of DNA replication factors and the phosphorylation of Cdc2 Tyr-15. The double deletion of clg1 and psl1 arrested meiotic initiation in pat1-114 mutant cells, similar to that of pef1-deficient cells. Meiotic progression was also slightly delayed in the pas1-deficient strain. Our results reveal that Pef1 regulates cyclin-coordinated meiotic progression.

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Loss of Meiotic Rereplication Block in Saccharomyces cerevisiae Cells Defective in Cdc28p Regulation

Eukaryotic Cell ◽

10.1128/ec.4.1.55-62.2005 ◽

2005 ◽

Vol 4 (1) ◽

pp. 55-62 ◽

Cited By ~ 10

Author(s):

Lyndi M. Rice ◽

Constantine Plakas ◽

Joseph T. Nickels

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Replication ◽

Kinase Inhibitor ◽

Yeast Cells ◽

Cyclin Dependent Kinase ◽

Loss Of Function ◽

Cyclin Dependent Kinase Inhibitor ◽

Phosphatase 2A ◽

Dependent Protein ◽

Mutant Cells

ABSTRACT Cdc28p is the major cyclin-dependent kinase in Saccharomyces cerevisiae. Its activity is required for blocking the reinitiation of DNA replication during mitosis. Here, we show that under conditions where Cdc28p activity is improperly regulated—either through the loss of function of the Schizosaccharomyces pombe wee1 ortholog Swe1p or through the expression of a dominant CDC28 allele, CDC28AF—diploid yeast cells are able to complete several rounds of premeiotic DNA replication within a single meiotic cell cycle. Moreover, a percentage of mutant cells exhibit a “multispore” phenotype, possessing the ability to package more than four spores within a single ascus. These multispored asci contain both even and odd numbers of viable spores. In order for meiotic rereplication and multispore formation to occur, cells must initiate homologous recombination and maintain proper chromosome cohesion during meiosis I. Rad9p- or Rad17p-dependent checkpoint mechanisms are not required for multispore formation and neither are the B-type cyclin Clb6p and the cyclin-dependent kinase inhibitor Sic1p. Finally, we present evidence of a possible role for a Cdc55p-dependent protein phosphatase 2A in initiating meiotic replication.

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Saccharomyces cerevisiaedeficient in the early anaphase release of Cdc14 can traverse anaphase I without ribosomal DNA disjunction and successfully complete meiosis

10.1101/2021.02.15.431250 ◽

2021 ◽

Author(s):

Christopher M. Yellman

Keyword(s):

Chromosome Segregation ◽

Ribosomal Dna ◽

Meiotic Chromosome ◽

Spindle Pole ◽

Cyclin Dependent Kinase ◽

Binding Partner ◽

Meiotic Progression ◽

Nuclear Domain ◽

Early Anaphase ◽

Mutant Cells

ABSTRACTEukaryotic meiosis is a specialized cell cycle involving two successive nuclear divisions that lead to the formation of haploid gametes. The phosphatase Cdc14 plays an essential role in meiosis as revealed in studies of the yeastSaccharomyces cerevisiae. Cdc14 is stored in the nucleolus, a sub-nuclear domain containing the ribosomal DNA, and its release is regulated by two distinct pathways, one acting in early anaphase I of meiosis and a second at the exit from meiosis II. The early anaphase release is thought to be important for disjunction of the ribosomal DNA, disassembly of the anaphase I spindle, spindle pole re-duplication and the counteraction of CDK, all of which are required for progression into meiosis II. The release of Cdc14 from its nucleolar binding partner Net1 is stimulated by phosphorylation of cyclin-dependent kinase sites in Net1, but the importance of that phospho-regulation in meiosis is not well understood. We inducednet1-6cdkmutant cells to enter meiosis and examined the localization of Cdc14 and various indicators of meiotic progression. Thenet1-6cdkmutations inhibit, but don’t fully prevent Cdc14 release, and they almost completely prevent disjunction of the ribosomal DNA during meiosis I. Failure to disjoin the ribosomal DNA is lethal in mitosis, and we expected the same to be true in meiosis. However, the cells were able to complete meiosis II, yielding the expected four meiotic products as viable spores. Therefore, all ribosomal DNA disjunction required for meiosis can occur in meiosis II. We discuss the implications of these findings for our understanding of meiotic chromosome segregation.

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The CRK2-CYC13 complex functions as an S-phase cyclin-dependent kinase to promote DNA replication in Trypanosoma brucei

BMC Biology ◽

10.1186/s12915-021-00961-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Kyu Joon Lee ◽

Ziyin Li

Keyword(s):

Dna Replication ◽

Trypanosoma Brucei ◽

S Phase ◽

Replication Initiation ◽

Cyclin Dependent Kinase ◽

Regulatory Pathway ◽

Dna Replication Initiation ◽

A Subunit ◽

Living Organisms ◽

Replication Factors

Abstract Background Faithful DNA replication is essential to maintain genomic stability in all living organisms, and the regulatory pathway for DNA replication initiation is conserved from yeast to humans. The evolutionarily ancient human parasite Trypanosoma brucei, however, lacks many of the conserved DNA replication factors and may employ unusual mechanisms for DNA replication. Neither the S-phase cyclin-dependent kinase (CDK) nor the regulatory pathway governing DNA replication has been previously identified in T. brucei. Results Here we report that CRK2 (Cdc2-related kinase 2) complexes with CYC13 (Cyclin13) and functions as an S-phase CDK to promote DNA replication in T. brucei. We further show that CRK2 phosphorylates Mcm3, a subunit of the Mcm2–7 sub-complex of the Cdc45-Mcm2–7-GINS complex, and demonstrate that Mcm3 phosphorylation by CRK2 facilitates interaction with Sld5, a subunit of the GINS sub-complex of the Cdc45-Mcm2–7-GINS complex. Conclusions These results identify the CRK2-CYC13 complex as an S-phase regulator in T. brucei and reveal its role in regulating DNA replication through promoting the assembly of the Cdc45-Mcm2–7-GINS complex.

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Hypoxic preconditioning reduces expression of the cyclin dependent kinase 5 in the post-ischemic neurons

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0309 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S309-S309

Author(s):

Svetlana Pundik ◽

W David Lust ◽

Jose Valerio ◽

Michael Buczek ◽

Randall D York ◽

...

Keyword(s):

Hypoxic Preconditioning ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase 5

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Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

International Journal of Pharmaceutical and Clinical Research ◽

10.25258/ijpcr.v9i6.8779 ◽

2017 ◽

Vol 9 (6) ◽

Author(s):

Sowmya Suri ◽

Rumana Waseem ◽

Seshagiri Bandi ◽

Sania Shaik

Keyword(s):

Molecular Docking ◽

3D Model ◽

Structural Features ◽

Docking Studies ◽

Amino Acid Residues ◽

Cyclin Dependent Kinase ◽

Ligand Complex ◽

Ligand Interaction ◽

Molecular Docking Studies ◽

Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

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