Centromeric Non-Coding RNAs: Conservation and Diversity in Function

Chromosome segregation is strictly regulated for the proper distribution of genetic material to daughter cells. During this process, mitotic chromosomes are pulled to both poles by bundles of microtubules attached to kinetochores that are assembled on the chromosomes. Centromeres are specific regions where kinetochores assemble. Although these regions were previously considered to be silent, some experimental studies have demonstrated that transcription occurs in these regions to generate non-coding RNAs (ncRNAs). These centromeric ncRNAs (cenRNAs) are involved in centromere functions. Here, we describe the currently available information on the functions of cenRNAs in several species.

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Mechanical Mechanisms of Chromosome Segregation

Cells ◽

10.3390/cells10020465 ◽

2021 ◽

Vol 10 (2) ◽

pp. 465

Author(s):

Maya I. Anjur-Dietrich ◽

Colm P. Kelleher ◽

Daniel J. Needleman

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Genetic Material ◽

Evolutionary Genetics ◽

Force Generation ◽

Coarse Grained ◽

Subcellular Structure ◽

Daughter Cells ◽

The Past ◽

The Future

Chromosome segregation—the partitioning of genetic material into two daughter cells—is one of the most crucial processes in cell division. In all Eukaryotes, chromosome segregation is driven by the spindle, a microtubule-based, self-organizing subcellular structure. Extensive research performed over the past 150 years has identified numerous commonalities and contrasts between spindles in different systems. In this review, we use simple coarse-grained models to organize and integrate previous studies of chromosome segregation. We discuss sites of force generation in spindles and fundamental mechanical principles that any understanding of chromosome segregation must be based upon. We argue that conserved sites of force generation may interact differently in different spindles, leading to distinct mechanical mechanisms of chromosome segregation. We suggest experiments to determine which mechanical mechanism is operative in a particular spindle under study. Finally, we propose that combining biophysical experiments, coarse-grained theories, and evolutionary genetics will be a productive approach to enhance our understanding of chromosome segregation in the future.

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Kinesin-Binding Protein (KBP) buffers the activity of KIF18A and KIF15 in mitosis to ensure accurate chromosome segregation

10.1101/343046 ◽

2018 ◽

Author(s):

Heidi L. H. Malaby ◽

Megan E. Dumas ◽

Ryoma Ohi ◽

Jason Stumpff

Keyword(s):

Motor Activity ◽

Chromosome Segregation ◽

Binding Protein ◽

Mitotic Chromosomes ◽

Microtubule Binding ◽

Daughter Cells ◽

Chromosome Alignment ◽

Segregation Of Chromosomes ◽

In Cells

ABSTRACTMitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here we demonstrate that Kinesin-Binding Protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule-binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation.SUMMARYKinesin-Binding Protein (KBP) is identified as a regulator of the kinesins KIF18A and KIF15 during mitosis. KBP buffers the activity of these motors to control chromosome alignment and spindle integrity in metaphase and prevent lagging chromosomes in anaphase.

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The Unresolved Problem of DNA Bridging

Genes ◽

10.3390/genes9120623 ◽

2018 ◽

Vol 9 (12) ◽

pp. 623 ◽

Cited By ~ 13

Author(s):

María Fernández-Casañas ◽

Kok-Lung Chan

Keyword(s):

Chromosome Segregation ◽

Genome Stability ◽

Genetic Material ◽

Genome Integrity ◽

Cellular Division ◽

Daughter Cells ◽

Dna Replication And Repair ◽

A Cell ◽

Chromosome Separation ◽

Last Stage

Accurate duplication and transmission of identical genetic information into offspring cells lies at the heart of a cell division cycle. During the last stage of cellular division, namely mitosis, the fully replicated DNA molecules are condensed into X-shaped chromosomes, followed by a chromosome separation process called sister chromatid disjunction. This process allows for the equal partition of genetic material into two newly born daughter cells. However, emerging evidence has shown that faithful chromosome segregation is challenged by the presence of persistent DNA intertwining structures generated during DNA replication and repair, which manifest as so-called ultra-fine DNA bridges (UFBs) during anaphase. Undoubtedly, failure to disentangle DNA linkages poses a severe threat to mitosis and genome integrity. This review will summarize the possible causes of DNA bridges, particularly sister DNA inter-linkage structures, in an attempt to explain how they may be processed and how they influence faithful chromosome segregation and the maintenance of genome stability.

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Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15

The Journal of Cell Biology ◽

10.1083/jcb.201806195 ◽

2019 ◽

Vol 218 (4) ◽

pp. 1218-1234 ◽

Cited By ~ 3

Author(s):

Heidi L.H. Malaby ◽

Megan E. Dumas ◽

Ryoma Ohi ◽

Jason Stumpff

Keyword(s):

Motor Activity ◽

Chromosome Segregation ◽

Binding Protein ◽

Mitotic Chromosomes ◽

Microtubule Binding ◽

Daughter Cells ◽

Segregation Of Chromosomes ◽

In Cells

Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation.

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Targeting mitotic chromosomes: a conserved mechanism to ensure viral genome persistence

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2008.1642 ◽

2009 ◽

Vol 276 (1662) ◽

pp. 1535-1544 ◽

Cited By ~ 21

Author(s):

Katherine M Feeney ◽

Joanna L Parish

Keyword(s):

Host Cell ◽

Genetic Material ◽

Membrane Integrity ◽

Mitotic Chromosomes ◽

Nuclear Retention ◽

Viral Genomes ◽

Daughter Cells ◽

Dna Damage Checkpoints ◽

Low Copy Number ◽

Dividing Cells

Viruses that maintain their genomes as extrachromosomal circular DNA molecules and establish infection in actively dividing cells must ensure retention of their genomes within the nuclear envelope in order to prevent genome loss. The loss of nuclear membrane integrity during mitosis dictates that paired host cell chromosomes are captured and organized by the mitotic spindle apparatus before segregation to daughter cells. This prevents inaccurate chromosomal segregation and loss of genetic material. A similar mechanism may also exist for the nuclear retention of extrachromosomal viral genomes or episomes during mitosis, particularly for genomes maintained at a low copy number in latent infections. It has been heavily debated whether such a mechanism exists and to what extent this mechanism is conserved among diverse viruses. Research over the last two decades has provided a wealth of information regarding the mechanisms by which specific tumour viruses evade mitotic and DNA damage checkpoints. Here, we discuss the similarities and differences in how specific viruses tether episomal genomes to host cell chromosomes during mitosis to ensure long-term persistence.

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Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B

Nucleic Acids Research ◽

10.1093/nar/gkaa449 ◽

2020 ◽

Vol 48 (12) ◽

pp. 6583-6596

Author(s):

Akiko Fujimura ◽

Yuki Hayashi ◽

Kazashi Kato ◽

Yuichiro Kogure ◽

Mutsuro Kameyama ◽

...

Keyword(s):

Chromosome Segregation ◽

Protein Complex ◽

Metaphase Plate ◽

Nucleolar Protein ◽

Aurora B ◽

Mitotic Progression ◽

Mitotic Chromosomes ◽

Nucleolar Proteins ◽

Chromatid Cohesion ◽

Wd Repeat

Abstract The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. During mitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.

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Dem Anfang auf der Spur — die Suche nach DNA-Replikationsursprüngen

BIOspektrum ◽

10.1007/s12268-021-1562-z ◽

2021 ◽

Vol 27 (3) ◽

pp. 246-249

Author(s):

Elisabeth Kruse ◽

Stephan Hamperl

Keyword(s):

Cell Division ◽

Dna Synthesis ◽

Genomic Dna ◽

Genetic Material ◽

Uniform Method ◽

Replication Origins ◽

Daughter Cells ◽

Origins Of Replication ◽

Mammalian Genomes ◽

Comprehensive Manner

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.

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The Regulatory Mechanism of Sexual Development in Decapod Crustaceans

Frontiers in Marine Science ◽

10.3389/fmars.2021.679687 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ardavan Farhadi ◽

Wenxiao Cui ◽

Huaiping Zheng ◽

Shengkang Li ◽

Yueling Zhang ◽

...

Keyword(s):

Gene Family ◽

Sexual Development ◽

Sexual Differentiation ◽

Regulatory Mechanism ◽

Regulation Mechanism ◽

Androgenic Gland ◽

Dead Box ◽

Males And Females ◽

Non Coding Rnas ◽

Available Information

Crustacean culture has been developing rapidly in various parts of the world. Therefore, it is important to understand their reproductive biology. Insulin-like androgenic gland hormone (IAG) secreted from the androgenic gland (AG) is widely accepted as a key regulator of sexual differentiation in male crustaceans. However, recently several sex-related genes (i.e., CFSH, DEAD-box family, Tra-2, Sxl, Dsx, Fem-1, Sox gene family, Foxl2, and Dmrt gene family) have been identified via transcriptomic analysis in crustaceans, indicating that sexual differentiation in crustaceans is more complicated than previously expected. It has been found that several non-coding RNAs (i.e., miRNAs, lncRNAs, and piRNAs) and IAG receptors may be involved in the sexual development of decapods. Identification and study of the regulation mechanism of sex-related genes, non-coding RNAs, and IAG receptors will provide valuable information regarding sexual development in decapods. In this review, the roles of hormonal and genetic factors in both males and females are discussed. In males, crustacean female sex hormone (CFSH), Sxl, Dmrt gene family, Dsx, Sox gene family, GEM, Fem-1, l-GnRH-III, and corazonin play important roles in IAG regulation in the “eyestalk-IAG-testis” endocrine axis. Unlike males, the regulation mechanism and interaction of sexual genes are relatively unknown in females. However, CFSH, IAG, Fem-1, FAMeT, Slo, UCHLs, Erk2, Cdc2, EGFR, Vg, VgR, and VIH seem to play crucial roles during ovarian development. This study summarizes the available information in the field, highlights gaps, and lays the foundations for further studies and a better understanding of the regulatory mechanism of sexual development in decapods.

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Genotoxic potential of nonsteroidal hormones

Veterinarski glasnik ◽

10.2298/vetgl1504245t ◽

2015 ◽

Vol 69 (3-4) ◽

pp. 245-258

Author(s):

Dijana Topalovic ◽

Lada Zivkovic ◽

Ninoslav Djelic ◽

Vladan Bajic ◽

Andrea Cabarkapa ◽

...

Keyword(s):

Oxidative Stress ◽

Genetic Material ◽

Experimental Studies ◽

Genotoxic Effect ◽

Common Mechanism ◽

Genotoxic Effects ◽

Specific Expression ◽

Study Results

Hormones are cellular products involved in the regulation of a large number of processes in living systems, and which by their actions affect the growth, function and metabolism of cells. Considering that hormones are compounds normally present in the organism, it is important to determine if they can, under certain circumstances, lead to genetic changes in the hereditary material. Numerous experimental studies in vitro and in vivo in different systems, from bacteria to mammals, dealt with the mutagenic and genotoxic effects of hormones. This work presents an overview of the research on genotoxic effects of non?steroidal hormones, although possible changes of genetic material under their influence have not still been known enough, and moreover, investigations on their genotoxic influence have given conflicting results. The study results show that mechanisms of genotoxic effect of nonsteroidal hormones are manifested through the increase of oxidative stress by arising reactive oxygen species. A common mechanism of ROS occurence in thyroid hormones and catecholamines is through metabolic oxidation of their phenolic groups. Manifestation of insulin genotoxic effect is based on production of ROS by activation of NADPH isophorms, while testing oxytocin showed absence of genotoxic effect. Considering that the investigations on genotoxicity of nonsteroidal hormones demonstrated both positive and negative results, the explanation of this discordance involve limitations of test systems themselves, different cell types or biological species used in the experiments, different level of reactivity in vitro and in vivo, as well as possible variations in a tissue-specific expression. Integrated, the provided data contribute to better understanding of genotoxic effect of nonsteroidal hormones and point out to the role and mode of action of these hormones in the process of occurring of effects caused by oxidative stress.

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MicroRNAs in the tumour microenvironment: big role for small players

Endocrine Related Cancer ◽

10.1530/erc-13-0119 ◽

2013 ◽

Vol 20 (5) ◽

pp. R257-R267 ◽

Cited By ~ 37

Author(s):

Patsy Soon ◽

Hippokratis Kiaris

Keyword(s):

Clinical Characteristics ◽

Experimental Studies ◽

Anticancer Therapy ◽

Tumour Microenvironment ◽

Regulatory Role ◽

Tumour Stroma ◽

Physiological Processes ◽

Non Coding Rnas

MicroRNAs (miRNAs) represent a class of small non-coding RNAs with an important regulatory role in various physiological processes as well as in several pathologies including cancers. It is noteworthy that recent evidence suggests that the regulatory role of miRNAs during carcinogenesis is not limited to the cancer cells but they are also implicated in the activation of tumour stroma and its transition into a cancer-associated state. Results from experimental studies involving cells culturedin vitroand mice bearing experimental tumours, corroborated by profiling of clinical cancers for miRNA expression, underline this role and identify miRNAs as a potent regulator of the crosstalk between cancer and stroma cells. Considering the fundamental role of the tumour microenvironment in determining both the clinical characteristics of the disease and the efficacy of anticancer therapy, miRNAs emerge as an attractive target bearing important prognostic and therapeutic significance during carcinogenesis. In this article, we will review the available results that underline the role of miRNAs in tumour stroma biology and emphasise their potential value as tools for the management of the disease.

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