The Aspergillus nidulans bncA1 mutation causes defects in the cell division cycle, nuclear movement and developmental morphogenesis

2001 ◽  
Vol 264 (5) ◽  
pp. 546-554 ◽  
Author(s):  
R. Castiglioni Pascon ◽  
A. A. Pizzirani-Kleiner ◽  
B. L. Miller
1992 ◽  
Vol 103 (3) ◽  
pp. 599-611 ◽  
Author(s):  
J.H. Doonan

Amenable to sophisticated genetic and molecular analysis, the simple filamentous fungus Aspergillus nidulans has provided some novel insights into the mechanisms and regulation of cell division. Mutational analysis has identified over fifty genes necessary for nuclear division, nuclear movement and cytokinesis. Molecular and cellular analysis of these mutants has led to the discovery of novel components of the cytoskeleton as well as to clarifying the role of established cytoskeletal proteins. Mutations leading to defects in the kinases (i.e. p34cdc2) and phosphatases (i.e. cdc25 and PP1), which are known to regulate mitosis in other eukaryotes, have been identified in Aspergillus. Additional, as yet novel, mitotic regulatory molecules, encoded by the nimA and bimE genes, have also been discovered in Aspergillus.


1999 ◽  
Vol 22 (3) ◽  
pp. 309-313 ◽  
Author(s):  
Cristina de Andrade-Monteiro ◽  
Nilce M. Martinez-Rossi

Microtubules are filaments composed of dimers of alpha- and beta-tubulins, which have a variety of functions in living cells. In fungi, the spindle pole bodies usually have been considered to be microtubule-organizing centers. We used the antimicrotubule drug Benomyl in block/release experiments to depolymerize and repolymerize microtubules in Aspergillus nidulans germlings to learn more about the microtubule nucleation process in this filamentous fungus. Twenty seconds after release from Benomyl short microtubules were formed from several bright (immunofluorescent) dots distributed along the germlings, suggesting that microtubule nucleation is randomly distributed in A. nidulans germlings. Since nuclear movement is dependent on microtubules in A. nidulans we analyzed whether mutants defective in nuclear distribution along the growing hyphae (nud mutants) have some obvious microtubule defect. Cytoplasmic, astral and spindle microtubules were present and appeared to be normal in all nud mutants. However, significant changes in the percentage of short versus long mitotic spindles were observed in nud mutants. This suggests that some of the nuclei of nud mutants do not reach the late stage of cell division at normal temperatures.


2001 ◽  
Vol 120 (5) ◽  
pp. A501-A501
Author(s):  
U HAUGWITZ ◽  
M WIEDMANN ◽  
K SPIESBACH ◽  
K ENGELAND ◽  
J MOSSNER

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 458
Author(s):  
Emmanuel Broni ◽  
Samuel K. Kwofie ◽  
Seth O. Asiedu ◽  
Whelton A. Miller ◽  
Michael D. Wilson

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.


2013 ◽  
Vol 87 (24) ◽  
pp. 13775-13784 ◽  
Author(s):  
O. Perwitasari ◽  
A. C. Torrecilhas ◽  
X. Yan ◽  
S. Johnson ◽  
C. White ◽  
...  

2002 ◽  
Vol 38 (17) ◽  
pp. 2290-2299 ◽  
Author(s):  
A Moretti ◽  
A Borriello ◽  
F Monno ◽  
M Criscuolo ◽  
A Rosolen ◽  
...  

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