scholarly journals The ATPase SRCAP is associated with the mitotic apparatus, uncovering novel molecular aspects of Floating-Harbor syndrome

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Giovanni Messina ◽  
Yuri Prozzillo ◽  
Francesca Delle Monache ◽  
Maria Virginia Santopietro ◽  
Maria Teresa Atterrato ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromatin Remodeling ◽  
Cell Biology ◽  
Cell Cycle Progression ◽  
Reverse Genetics ◽  
Genetic Diseases ◽  
Main Function ◽  
Histone H2a ◽  
Mitotic Apparatus ◽  
Floating Harbor Syndrome

Abstract Background A variety of human genetic diseases is known to be caused by mutations in genes encoding chromatin factors and epigenetic regulators, such as DNA or histone modifying enzymes and members of ATP-dependent chromatin remodeling complexes. Floating-Harbor syndrome is a rare genetic disease affecting human development caused by dominant truncating mutations in the SRCAP gene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. The main function of the SRCAP complex is to promote the exchange of histone H2A with the H2A.Z variant. According to the canonical role played by the SRCAP protein in epigenetic regulation, the Floating-Harbor syndrome is thought to be a consequence of chromatin perturbations. However, additional potential physiological functions of SRCAP have not been sufficiently explored. Results We combined cell biology, reverse genetics, and biochemical approaches to study the subcellular localization of the SRCAP protein and assess its involvement in cell cycle progression in HeLa cells. Surprisingly, we found that SRCAP associates with components of the mitotic apparatus (centrosomes, spindle, midbody), interacts with a plethora of cytokinesis regulators, and positively regulates their recruitment to the midbody. Remarkably, SRCAP depletion perturbs both mitosis and cytokinesis. Similarly, DOM-A, the functional SRCAP orthologue in Drosophila melanogaster, is found at centrosomes and the midbody in Drosophila cells, and its depletion similarly affects both mitosis and cytokinesis. Conclusions Our findings provide first evidence suggesting that SRCAP plays previously undetected and evolutionarily conserved roles in cell division, independent of its functions in chromatin regulation. SRCAP may participate in two different steps of cell division: by ensuring proper chromosome segregation during mitosis and midbody function during cytokinesis. Moreover, our findings emphasize a surprising scenario whereby alterations in cell division produced by SRCAP mutations may contribute to the onset of Floating-Harbor syndrome.

scholarly journals ATPase SRCAP is a new player in cell division, uncovering molecular aspects of Floating-Harbor syndrome

2020 ◽  
Author(s):  
Giovanni Messina ◽  
Yuri Prozzillo ◽  
Francesca Delle Monache ◽  
Maria Virginia Santopietro ◽  
Maria Teresa Atterrato ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromatin Remodeling ◽  
Catalytic Subunit ◽  
Current View ◽  
Mitotic Apparatus ◽  
Direct Role ◽  
The Core ◽  
Chromatin Remodeling Complex ◽  
Evolutionarily Conserved ◽  
Floating Harbor Syndrome

AbstractFloating-Harbor syndrome (FHS) is a rare genetic disease affecting human development caused by heterozygous truncating mutations in the Srcap gene, which encodes the ATPase SRCAP, the core catalytic subunit of the homonymous chromatin-remodeling complex. Using a combined approach, we studied the involvement of SRCAP protein in cell cycle progression in HeLa cells. In addition to the canonical localization in interphase nuclei, both SRCAP and its Drosophila orthologue DOMINO-A localized to the mitotic apparatus after nuclear envelope breakdown. Moreover, SRCAP and DOMINO-A depletion impaired mitosis and cytokinesis in human and Drosophila cells, respectively. Importantly, SRCAP interacted with several cytokinesis regulators at telophase, strongly supporting a direct role in cytokinesis, independent of its chromatin remodeling functions. Our results provide clues about previously undetected, evolutionarily conserved roles of SRCAP in ensuring proper mitosis and cytokinesis. We propose that perturbations in cell division contribute to the onset of developmental defects characteristic of FHS.SummarySignificance statementSrcap is the causative gene of the rare Floating Harbor syndrome (FHS). It encodes the ATPase SRCAP, the core catalytic subunit of the homonymous multiprotein chromatin-remodeling complex in humans, which promotes the exchange of canonical histone H2A with the H2A.Z variant. According to the current view on SRCAP protein functions, FHS is caused by chromatin remodeling defects. Our findings suggest that, in addition to the established function as epigenetic regulator, SRCAP plays previously undetected and evolutionarily conserved roles in cell division. Hence, we propose that perturbations in cell division produced by SRCAP mutations are important causative factors co-occurring at the onset of FHS.

scholarly journals In Vivo Silencing of Genes Coding for dTip60 Chromatin Remodeling Complex Subunits Affects Polytene Chromosome Organization and Proper Development in Drosophila melanogaster

2021 ◽  
Vol 22 (9) ◽  
pp. 4525
Author(s):  
Yuri Prozzillo ◽  
Stefano Cuticone ◽  
Diego Ferreri ◽  
Gaia Fattorini ◽  
Giovanni Messina ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Chromatin Remodeling ◽  
Cell Biology ◽  
Reverse Genetics ◽  
Developmentally Regulated ◽  
Chromatin Remodeling Complex ◽  
Chromatin Remodeling Complexes ◽  
Histone Modifying Enzymes ◽  
Classical Genetics

Chromatin organization is developmentally regulated by epigenetic changes mediated by histone-modifying enzymes and chromatin remodeling complexes. In Drosophila melanogaster, the Tip60 chromatin remodeling complex (dTip60) play roles in chromatin regulation, which are shared by evolutionarily-related complexes identified in animal and plants. Recently, it was found that most subunits previously assigned to the dTip60 complex are shared by two related complexes, DOM-A.C and DOM-B.C, defined by DOM-A and DOM-B isoforms, respectively. In this work, we combined classical genetics, cell biology, and reverse genetics approaches to further investigate the biological roles played during Drosophila melanogaster development by a number of subunits originally assigned to the dTip60 complex.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

scholarly journals Plant evolution driven by interactions with symbiotic and pathogenic microbes

Science ◽  
2021 ◽  
Vol 371 (6531) ◽  
pp. eaba6605 ◽  
Author(s):  
Pierre-Marc Delaux ◽  
Sebastian Schornack
Keyword(s):  
Cell Biology ◽  
Genetic Basis ◽  
Reverse Genetics ◽  
Molecular Mechanisms ◽  
Plant Evolution ◽  
Symbiotic Microorganisms ◽  
Protection Mechanisms ◽  
Evolutionary Trajectories ◽  
Microbe Interactions ◽  
Pathogenic Microbes

During 450 million years of diversification on land, plants and microbes have evolved together. This is reflected in today’s continuum of associations, ranging from parasitism to mutualism. Through phylogenetics, cell biology, and reverse genetics extending beyond flowering plants into bryophytes, scientists have started to unravel the genetic basis and evolutionary trajectories of plant-microbe associations. Protection against pathogens and support of beneficial, symbiotic, microorganisms are sustained by a blend of conserved and clade-specific plant mechanisms evolving at different speeds. We propose that symbiosis consistently emerges from the co-option of protection mechanisms and general cell biology principles. Exploring and harnessing the diversity of molecular mechanisms used in nonflowering plant-microbe interactions may extend the possibilities for engineering symbiosis-competent and pathogen-resilient crops.

scholarly journals The Cell Division Cycle of Euglena gracilis Indicates That the Level of Circadian Plasticity to the External Light Regime Changes in Prolonged-Stationary Cultures

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1475
Author(s):  
Shota Kato ◽  
Hong Gil Nam
Keyword(s):  
Cell Division ◽  
Circadian Rhythms ◽  
Euglena Gracilis ◽  
Cell Cycle Progression ◽  
Light Signal ◽  
Cell Division Cycle ◽  
Regime Changes ◽  
Fitness Advantage ◽  
Subjective Night ◽  
Free Running

In unicellular photosynthetic organisms, circadian rhythm is tightly linked to gating of cell cycle progression, and is entrained by light signal. As several organisms obtain a fitness advantage when the external light/dark cycle matches their endogenous period, and aging alters circadian rhythms, senescence phenotypes of the microalga Euglena gracilis of different culture ages were characterized with respect to the cell division cycle. We report here the effects of prolonged-stationary-phase conditions on the cell division cycles of E. gracilis under non-24-h light/dark cycles (T-cycles). Under T-cycles, cells established from 1-month-old and 2-month-old cultures produced lower cell concentrations after cultivation in the fresh medium than cells from 1-week-old culture. This decrease was not due to higher concentrations of dead cells in the populations, suggesting that cells of different culture ages differ in their capacity for cell division. Cells from 1-week-old cultures had a shorter circadian period of their cell division cycle under shortened T-cycles than aged cells. When algae were transferred to free-running conditions after entrainment to shortened T-cycles, the young cells showed the peak growth rate at a time corresponding to the first subjective night, but the aged cells did not. This suggests that circadian rhythms are more plastic in younger E. gracilis cells.

Asymmetric cell division in fucoid algae: a role for cortical adhesions in alignment of the mitotic apparatus

2001 ◽  
Vol 114 (23) ◽  
pp. 4319-4328
Author(s):  
Sherryl R. Bisgrove ◽  
Darryl L. Kropf
Keyword(s):  
Cell Division ◽  
Asymmetric Cell Division ◽  
Cell Cortex ◽  
Mitotic Apparatus ◽  
Pharmacological Agents ◽  
Division Plane ◽  
Adhesion Sites ◽  
Spindle Poles ◽  
Pelvetia Compressa ◽  
Two Phases

The first cell division in zygotes of the fucoid brown alga Pelvetia compressa is asymmetric and we are interested in the mechanism controlling the alignment of this division. Since the division plane bisects the mitotic apparatus, we investigated the timing and mechanism of spindle alignments. Centrosomes, which give rise to spindle poles, aligned with the growth axis in two phases – a premetaphase rotation of the nucleus and centrosomes followed by a postmetaphase alignment that coincided with the separation of the mitotic spindle poles during anaphase and telophase. The roles of the cytoskeleton and cell cortex in the two phases of alignment were analyzed by treatment with pharmacological agents. Treatments that disrupted cytoskeleton or perturbed cortical adhesions inhibited pre-metaphase alignment and we propose that this rotational alignment is effected by microtubules anchored at cortical adhesion sites. Postmetaphase alignment was not affected by any of the treatments tested, and may be dependent on asymmetric cell morphology.

scholarly journals Analysis of Cell Cycle and Replication of Mouse Macrophages afterIn VivoandIn VitroCryptococcus neoformans Infection Using Laser Scanning Cytometry

2012 ◽  
Vol 80 (4) ◽  
pp. 1467-1478 ◽  
Author(s):  
Carolina Coelho ◽  
Lydia Tesfa ◽  
Jinghang Zhang ◽  
Johanna Rivera ◽  
Teresa Gonçalves ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cytotoxic Effect ◽  
Laser Scanning ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Content Type ◽  
Cycle Arrest ◽  
Laser Scanning Cytometry

ABSTRACTWe investigated the outcome of the interaction ofCryptococcus neoformanswith murine macrophages using laser scanning cytometry (LSC). Previous results in our lab had shown that phagocytosis ofC. neoformanspromoted cell cycle progression. LSC allowed us to simultaneously measure the phagocytic index, macrophage DNA content, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation such that it was possible to study host cell division as a function of phagocytosis. LSC proved to be a robust, reliable, and high-throughput method for quantifying phagocytosis. Phagocytosis ofC. neoformanspromoted cell cycle progression, but infected macrophages were significantly less likely to complete mitosis. Hence, we report a new cytotoxic effect associated with intracellularC. neoformansresidence that manifested itself in impaired cell cycle completion as a consequence of a block in the G2/M stage of the mitotic cell cycle. Cell cycle arrest was not due to increased cell membrane permeability or DNA damage. We investigated alveolar macrophage replicationin vivoand demonstrated that these cells are capable of low levels of cell division in the presence or absence ofC. neoformansinfection. In summary, we simultaneously studied phagocytosis, the cell cycle state of the host cell and pathogen-mediated cytotoxicity, and our results demonstrate a new cytotoxic effect ofC. neoformansinfection on murine macrophages: fungus-induced cell cycle arrest. Finally, we provide evidence for alveolar macrophage proliferationin vivo.

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