scholarly journals Shugoshin: From the Perspective of Clinical Disorders

BioChem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 51-59
Author(s):  
Ravinder Kumar ◽  
Meenakshi Agarwal

Proper and timely segregation of the cellular genome is a prime requirement of all cell division programs. Mis-segregation of chromosomes and the resulting aneuploidy lead to several clinical consequences. Over the years, shugoshin has emerged as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or an altered level of shugoshin is reported in several human malignancies; as a result, shugoshin is now emerging as an important tumor-associated gene and a possible target for cancer therapy. Apart from its role in cancer, recent studies have also shown the involvement of shugoshin in several other clinical disorders. In this review, we aim to highlight the clinical relevance of shugoshin.

Author(s):  
Ravinder Kumar ◽  
Meenakshi Agarwal

Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.


Author(s):  
Samah Bodowara ◽  
Fauzia El Garaboli ◽  
Salem El shatshat

The present study aimed to measure the cytotoxic and genotoxic effect of the bark of A. nilotica extract. Allium cepa assay was used to find out the effect of A. nilotica extract on chromosome structure and behavior during cell division. The root tips meristem cells were treated with different concentration of A. nilotica bark aqueous extract (0.1, 0.01 and 0.001mg/ml) for 4, 6, 12 and 24 hours, respectively. Cytological analysis revealed decreasing in cell division in all used concentration especially at high ones. The obtained results indicate that aqueous extracts of A. nilotica plant have the ability to decrease the (MI%) values with increasing the concentration at (P<0.005). All treatments have caused different kind of mitotic abnormalities and chromosomal aberrations, such as: change percentage of mitotic phases, C-mitosis, stickiness, chromosome bridges, Micronucleus and vagrant chromosome. The action of A. nilotica bark extract on the genetic material led to decrease in dividing cells number which was concentration and time depended. This inhibition of cell division was due to disturbances in nucleus as a result of inhibition of DNA synthesis. KEY WORDS: Allium cepa assay: A. nilotica: Chromosomal aberrations; MI.


2020 ◽  
Vol 4 (1) ◽  
pp. 257-278 ◽  
Author(s):  
Natalie L. Curtis ◽  
Gian Filippo Ruda ◽  
Paul Brennan ◽  
Victor M. Bolanos-Garcia

The mitotic spindle assembly checkpoint (SAC) is an intricate cell signaling system that ensures the high fidelity and timely segregation of chromosomes during cell division. Mistakes in this process can lead to the loss, gain, or rearrangement of the genetic material. Gross chromosomal aberrations are usually lethal but can cause birth and development defects as well as cancer. Despite advances in the identification of SAC protein components, important details of the interactions underpinning chromosome segregation regulation remain to be established. This review discusses the current understanding of the function, structure, mode of regulation, and dynamics of the assembly and disassembly of SAC subcomplexes, which ultimately safeguard the accurate transmission of a stable genome to descendants. We also discuss how diverse oncoviruses take control of human cell division by exploiting the SAC and the potential of this signaling circuitry as a pool of drug targets to develop effective cancer therapies.


1998 ◽  
Vol 9 (8) ◽  
pp. 2037-2049 ◽  
Author(s):  
William B. Raich ◽  
Adrienne N. Moran ◽  
Joel H. Rothman ◽  
Jeff Hardin

Members of the MKLP1 subfamily of kinesin motor proteins localize to the equatorial region of the spindle midzone and are capable of bundling antiparallel microtubules in vitro. Despite these intriguing characteristics, it is unclear what role these kinesins play in dividing cells, particularly within the context of a developing embryo. Here, we report the identification of a null allele ofzen-4, an MKLP1 homologue in the nematodeCaenorhabditis elegans, and demonstrate that ZEN-4 is essential for cytokinesis. Embryos deprived of ZEN-4 form multinucleate single-celled embryos as they continue to cycle through mitosis but fail to complete cell division. Initiation of the cytokinetic furrow occurs at the normal time and place, but furrow propagation halts prematurely. Time-lapse recordings and microtubule staining reveal that the cytokinesis defect is preceded by the dissociation of the midzone microtubules. We show that ZEN-4 protein localizes to the spindle midzone during anaphase and persists at the midbody region throughout cytokinesis. We propose that ZEN-4 directly cross-links the midzone microtubules and suggest that these microtubules are required for the completion of cytokinesis.


BIOspektrum ◽  
2021 ◽  
Vol 27 (3) ◽  
pp. 246-249
Author(s):  
Elisabeth Kruse ◽  
Stephan Hamperl

AbstractTimely and accurate duplication of DNA prior to cell division is a prerequisite for propagation of the genetic material to both daughter cells. DNA synthesis initiates at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, a uniform method that identifies origins of replication in a comprehensive manner is still missing. Here, we present currently available and discuss new approaches to map replication origins in mammalian genomes.


Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1267-1276
Author(s):  
Katayoun Afshar ◽  
Pierre Gönczy ◽  
Stephen DiNardo ◽  
Steven A Wasserman

Abstract A number of fundamental processes comprise the cell division cycle, including spindle formation, chromosome segregation, and cytokinesis. Our current understanding of these processes has benefited from the isolation and analysis of mutants, with the meiotic divisions in the male germline of Drosophila being particularly well suited to the identification of the required genes. We show here that the fumble (fbl) gene is required for cell division in Drosophila. We find that dividing cells in fbl-deficient testes exhibit abnormalities in bipolar spindle organization, chromosome segregation, and contractile ring formation. Cytological analysis of larval neuroblasts from null mutants reveals a reduced mitotic index and the presence of polyploid cells. Molecular analysis demonstrates that fbl encodes three protein isoforms, all of which contain a domain with high similarity to the pantothenate kinases of A. nidulans and mouse. The largest Fumble isoform is dispersed in the cytoplasm during interphase, concentrates around the spindle at metaphase, and localizes to the spindle midbody at telophase. During early embryonic development, the protein localizes to areas of membrane deposition and/or rearrangement, such as the metaphase and cellularization furrows. Given the role of pantothenate kinase in production of Coenzyme A and in phospholipid biosynthesis, this pattern of localization is suggestive of a role for fbl in membrane synthesis. We propose that abnormalities in synthesis and redistribution of membranous structures during the cell division cycle underlie the cell division defects in fbl mutant cells.


1983 ◽  
Vol 60 (1) ◽  
pp. 137-156
Author(s):  
L.A. Hufnagel

A freeze-fracture analysis of early neogenesis of somatic and oral cilia of Tetrahymena was conducted using exponentially grown cultures and also cells induced to undergo oral reorganization. In this report, presumptive ciliary domains (PCDs), sites of future outgrowth of somatic cilia, are identified and their membrane structure is described in detail. The fairy ring, an array of membrane particles that occurs within the PCD and appears to be a precursor of the ciliary necklace, is described. A sequence of early stages in the formation of the ciliary necklace of somatic cilia is deduced from topographical information and membrane particle arrangements and numbers. Evidence is presented that basal bodies are seated at the cell surface prior to initiation of necklace assembly and a possible role for the basal body in necklace assembly is suggested. In dividing cells, new oral cilia grow out prior to orientation of cilia-parasomal sac complexes relative to cell axes. In dividing cells and during oral reorganization, new cilia also develop prior to their alignment into membranelles. Thus, growth of cilia is independent of their spatial orientation. Fairy rings were not observed during oral reorganization. During cell division, proliferation of new cilia is accompanied by the formation of a network of junctions between a cortical system of membranous cisternae, the cortical ‘alveoli’. These interalveolar junctions may serve as tracks for early positioning and orientation of new oral basal bodies.


Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4623-4633 ◽  
Author(s):  
K. Gallagher ◽  
L.G. Smith

In plant cells, cytokinesis depends on a cytoskeletal structure called a phragmoplast, which directs the formation of a new cell wall between daughter nuclei after mitosis. The orientation of cell division depends on guidance of the phragmoplast during cytokinesis to a cortical site marked throughout prophase by another cytoskeletal structure called a preprophase band. Asymmetrically dividing cells become polarized and form asymmetric preprophase bands prior to mitosis; phragmoplasts are subsequently guided to these asymmetric cortical sites to form daughter cells of different shapes and/or sizes. Here we describe two new recessive mutations, discordia1 (dcd1) and discordia2 (dcd2), which disrupt the spatial regulation of cytokinesis during asymmetric cell divisions. Both mutations disrupt four classes of asymmetric cell divisions during the development of the maize leaf epidermis, without affecting the symmetric divisions through which most epidermal cells arise. The effects of dcd mutations on asymmetric cell division can be mimicked by cytochalasin D treatment, and divisions affected by dcd1 are hypersensitive to the effects of cytochalasin D. Analysis of actin and microtubule organization in these mutants showed no effect of either mutation on cell polarity, or on formation and localization of preprophase bands and spindles. In mutant cells, phragmoplasts in asymmetrically dividing cells are structurally normal and are initiated in the correct location, but often fail to move to the position formerly occupied by the preprophase band. We propose that dcd mutations disrupt an actin-dependent process necessary for the guidance of phragmoplasts during cytokinesis in asymmetrically dividing cells.


2018 ◽  
Author(s):  
Kiran Lalwani ◽  
Shivani Sheth ◽  
Inayatullah Sheikh ◽  
Afzal Ansari ◽  
Fulesh Kunwar ◽  
...  

Chromosomal translocations involve exchange of genetic material between non- homologous chromosomes leading to the formation of a fusion gene with altered function. The clinical consequences of non-random and recurrent chromosomal translocations have been so well understood in carcinogenesis that they serve as diagnostic and prognostic markers and also help in therapy decisions, mainly in leukemia and lymphoma. However, the molecular mechanisms underlying these recurrent genetic exchanges are yet to be understood. Various approaches employed include the extent of the vicinity of the partner chromosomes in the nucleus, DNA sequences at the breakpoints, etc. The present study addresses the stability of DNA sequences at the breakpoint regions using in-silico approach in terms of physicochemical properties such as; AT%, flexibility, melting temperature, enthalpy, entropy, stacking energy and free energy. Changes in these properties may lead to instability of DNA which could affect gene expression in particular and genome organization in general. Our study indicates that the fusion sequences are comparatively more unstable and hence, more prone to breakage. Current study along with others could lead to developing a model for predicting breakage prone genomic regions using this novel in-silico approach.


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