The conjugation process in the jelly fungus Sirobasidium magnum

The formation of conjugation tubes in yeast cells of the jelly fungus Sirobasidium magnum (Basidiomycotina) was shown to be mediated by diffusible pheromones which passed through dialysis membranes of 12 000 to 14 000 daltons molecular exclusion limit. The yeast cells were responsive to pheromone only in G1 of the cell division cycle. Although caffeine induced morphological abnormalities in the yeast cells and although conjugation tube formation was catabolically repressed by glucose, evidence for the involvement of cyclic nucleotides as secondary messengers in conjugation tube induction was negative. There was some evidence for the presence of a conjugation inhibitor(s).

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Regulation of genes for the cdc25 phosphatases is important for checkpoint control during the cell division cycle

Gastroenterology ◽

10.1016/s0016-5085(01)82489-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A501-A501

Author(s):

U HAUGWITZ ◽

M WIEDMANN ◽

K SPIESBACH ◽

K ENGELAND ◽

J MOSSNER

Keyword(s):

Cell Division ◽

Cell Division Cycle ◽

Checkpoint Control

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Identification of Cell Division Cycle 20 as a Candidate Biomarker and Potential Therapeutic Target in Bladder Cancer Using Integrated Bioinformatics Analysis

SSRN Electronic Journal ◽

10.2139/ssrn.3284177 ◽

2018 ◽

Author(s):

Pei-lin Shen ◽

Xue-jun He ◽

Lin Lan ◽

Ming-en Lin ◽

Ying-kai Hong

Keyword(s):

Bladder Cancer ◽

Cell Division ◽

Therapeutic Target ◽

Bioinformatics Analysis ◽

Cell Division Cycle ◽

Potential Therapeutic Target

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A Molecular Modeling Approach to Identify Potential Antileishmanial Compounds Against the Cell Division Cycle (cdc)-2-Related Kinase 12 (CRK12) Receptor of Leishmania donovani

Biomolecules ◽

10.3390/biom11030458 ◽

2021 ◽

Vol 11 (3) ◽

pp. 458

Author(s):

Emmanuel Broni ◽

Samuel K. Kwofie ◽

Seth O. Asiedu ◽

Whelton A. Miller ◽

Michael D. Wilson

Keyword(s):

Natural Products ◽

Cell Division ◽

Leishmania Donovani ◽

Therapeutic Potential ◽

Neglected Tropical Diseases ◽

Binding Pocket ◽

Cell Division Cycle ◽

World Health ◽

Atp Binding ◽

African Flora

The huge burden of leishmaniasis caused by the trypanosomatid protozoan parasite Leishmania is well known. This illness was included in the list of neglected tropical diseases targeted for elimination by the World Health Organization. However, the increasing evidence of resistance to existing antimonial drugs has made the eradication of the disease difficult to achieve, thus warranting the search for new drug targets. We report here studies that used computational methods to identify inhibitors of receptors from natural products. The cell division cycle-2-related kinase 12 (CRK12) receptor is a plausible drug target against Leishmania donovani. This study modelled the 3D molecular structure of the L. donovani CRK12 (LdCRK12) and screened for small molecules with potential inhibitory activity from African flora. An integrated library of 7722 African natural product-derived compounds and known inhibitors were screened against the LdCRK12 using AutoDock Vina after performing energy minimization with GROMACS 2018. Four natural products, namely sesamin (NANPDB1649), methyl ellagic acid (NANPDB1406), stylopine (NANPDB2581), and sennecicannabine (NANPDB6446) were found to be potential LdCRK12 inhibitory molecules. The molecular docking studies revealed two compounds NANPDB1406 and NANPDB2581 with binding affinities of −9.5 and −9.2 kcal/mol, respectively, against LdCRK12 which were higher than those of the known inhibitors and drugs, including GSK3186899, amphotericin B, miltefosine, and paromomycin. All the four compounds were predicted to have inhibitory constant (Ki) values ranging from 0.108 to 0.587 μM. NANPDB2581, NANPDB1649 and NANPDB1406 were also predicted as antileishmanial with Pa and Pi values of 0.415 and 0.043, 0.391 and 0.052, and 0.351 and 0.071, respectively. Molecular dynamics simulations coupled with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) computations reinforced their good binding mechanisms. Most compounds were observed to bind in the ATP binding pocket of the kinase domain. Lys488 was predicted as a key residue critical for ligand binding in the ATP binding pocket of the LdCRK12. The molecules were pharmacologically profiled as druglike with inconsequential toxicity. The identified molecules have scaffolds that could form the backbone for fragment-based drug design of novel leishmanicides but warrant further studies to evaluate their therapeutic potential.

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Comparison of dose-response curves for alpha factor-induced cell division arrest, agglutination, and projection formation of yeast cells. Implication for the mechanism of alpha factor action.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)43996-2 ◽

1983 ◽

Vol 258 (22) ◽

pp. 13849-13856 ◽

Cited By ~ 7

Author(s):

S A Moore

Keyword(s):

Cell Division ◽

Dose Response ◽

Yeast Cells ◽

Response Curves ◽

Alpha Factor ◽

Dose Response Curves

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Replicative Aging in Pathogenic Fungi

Journal of Fungi ◽

10.3390/jof7010006 ◽

2020 ◽

Vol 7 (1) ◽

pp. 6

Author(s):

Somanon Bhattacharya ◽

Tejas Bouklas ◽

Bettina C. Fries

Keyword(s):

Cell Division ◽

Candida Glabrata ◽

Asymmetric Cell Division ◽

Pathogenic Fungi ◽

Yeast Cells ◽

Candida Auris ◽

Replicative Aging ◽

Yeast Saccharomyces Cerevisiae ◽

Phenotypic Variations ◽

Systemic Infections

Candida albicans, Candida auris, Candida glabrata, and Cryptococcus neoformans are pathogenic yeasts which can cause systemic infections in immune-compromised as well as immune-competent individuals. These yeasts undergo replicative aging analogous to a process first described in the nonpathogenic yeast Saccharomyces cerevisiae. The hallmark of replicative aging is the asymmetric cell division of mother yeast cells that leads to the production of a phenotypically distinct daughter cell. Several techniques to study aging that have been pioneered in S. cerevisiae have been adapted to study aging in other pathogenic yeasts. The studies indicate that aging is relevant for virulence in pathogenic fungi. As the mother yeast cell progressively ages, every ensuing asymmetric cell division leads to striking phenotypic changes, which results in increased antifungal and antiphagocytic resistance. This review summarizes the various techniques that are used to study replicative aging in pathogenic fungi along with their limitations. Additionally, the review summarizes some key phenotypic variations that have been identified and are associated with changes in virulence or resistance and thus promote persistence of older cells.

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