At the Interface Between Signaling and Executing Anaphase—Cdc14 and the FEAR Network
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Timing of Centrosome Separation Is Important for Accurate Chromosome Segregation
M BoC | ARTICLE Timing of centrosome separation is important for accurate chromosome segregation William T. Silkwortha, Isaac K. Nardia,*, Raja Paulb, Alex Mogilnerc, and Daniela Ciminia aDepartment of Biological Sciences, Virginia Tech, Blacksburg, VA 24061; bIndian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India; cDepartment of Neurobiology, Physiology and Behavior and Department of Mathematics, University of California, Davis, Davis, CA 95616 ABSTRACT Spindle assembly, establishment of kinetochore attachment, and sister chroma- Monitoring Editor tid separation must occur during mitosis in a highly coordinated fashion to ensure accurate Yixian Zheng chromosome segregation. In most vertebrate cells, the nuclear envelope must break down to Carnegie Institution allow interaction between microtubules of the mitotic spindle and the kinetochores. It was Received: Feb 2, 2011 previously shown that nuclear envelope breakdown (NEB) is not coordinated with centrosome Revised: Nov 17, 2011 separation and that centrosome separation can be either complete at the time of NEB or can Accepted: Nov 22, 2011 be completed after NEB. In this study, we investigated whether the timing of centrosome separation affects subsequent mitotic events such as establishment of kinetochore attach- ment or chromosome segregation. We used a combination of experimental and computa- tional approaches to investigate kinetochore attachment and chromosome segregation in cells with complete versus incomplete spindle pole separation at NEB. We found that cells with incomplete spindle pole separation exhibit higher rates of kinetochore misattachments and chromosome missegregation than cells that complete centrosome separation before NEB. Moreover, our mathematical model showed that two spindle poles in close proximity do not “search” the entire cellular space, leading to formation of large numbers of syntelic at- tachments, which can be an intermediate stage in the formation of merotelic kinetochores. -
Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes
G C A T T A C G G C A T genes Article Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes Filip Pajpach , Linda Shearwin-Whyatt and Frank Grützner * School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; fi[email protected] (F.P.); [email protected] (L.S.-W.) * Correspondence: [email protected] Abstract: Chromosome segregation at mitosis and meiosis is a highly dynamic and tightly regulated process that involves a large number of components. Due to the fundamental nature of chromosome segregation, many genes involved in this process are evolutionarily highly conserved, but duplica- tions and functional diversification has occurred in various lineages. In order to better understand the evolution of genes involved in chromosome segregation in mammals, we analyzed some of the key components in the basal mammalian lineage of egg-laying mammals. The chromosome passenger complex is a multiprotein complex central to chromosome segregation during both mitosis and meio- sis. It consists of survivin, borealin, inner centromere protein, and Aurora kinase B or C. We confirm the absence of Aurora kinase C in marsupials and show its absence in both platypus and echidna, which supports the current model of the evolution of Aurora kinases. High expression of AURKBC, an ancestor of AURKB and AURKC present in monotremes, suggests that this gene is performing all necessary meiotic functions in monotremes. Other genes of the chromosome passenger complex complex are present and conserved in monotremes, suggesting that their function has been preserved Citation: Pajpach, F.; in mammals. -
GENETICS and GENOMICS Ed
GENETICS AND GENOMICS Ed. Csaba Szalai, PhD GENETICS AND GENOMICS Editor: Csaba Szalai, PhD, university professor Authors: Chapter 1: Valéria László Chapter 2, 3, 4, 6, 7: Sára Tóth Chapter 5: Erna Pap Chapter 8, 9, 10, 11, 12, 13, 14: Csaba Szalai Chapter 15: András Falus and Ferenc Oberfrank Keywords: Mitosis, meiosis, mutations, cytogenetics, epigenetics, Mendelian inheritance, genetics of sex, developmental genetics, stem cell biology, oncogenetics, immunogenetics, human genomics, genomics of complex diseases, genomic methods, population genetics, evolution genetics, pharmacogenomics, nutrigenetics, gene environmental interaction, systems biology, bioethics. Summary The book contains the substance of the lectures and partly of the practices of the subject of ‘Genetics and Genomics’ held in Semmelweis University for medical, pharmacological and dental students. The book does not contain basic genetics and molecular biology, but rather topics from human genetics mainly from medical point of views. Some of the 15 chapters deal with medical genetics, but the chapters also introduce to the basic knowledge of cell division, cytogenetics, epigenetics, developmental genetics, stem cell biology, oncogenetics, immunogenetics, population genetics, evolution genetics, nutrigenetics, and to a relative new subject, the human genomics and its applications for the study of the genomic background of complex diseases, pharmacogenomics and for the investigation of the genome environmental interactions. As genomics belongs to sytems biology, a chapter introduces to basic terms of systems biology, and concentrating on diseases, some examples of the application and utilization of this scientific field are also be shown. The modern human genetics can also be associated with several ethical, social and legal issues. The last chapter of this book deals with these issues. -
Analysis of the Stability of 70 Housekeeping Genes During Ips Reprogramming Yulia Panina1,2*, Arno Germond1 & Tomonobu M
www.nature.com/scientificreports OPEN Analysis of the stability of 70 housekeeping genes during iPS reprogramming Yulia Panina1,2*, Arno Germond1 & Tomonobu M. Watanabe1 Studies on induced pluripotent stem (iPS) cells highly rely on the investigation of their gene expression which requires normalization by housekeeping genes. Whether the housekeeping genes are stable during the iPS reprogramming, a transition of cell state known to be associated with profound changes, has been overlooked. In this study we analyzed the expression patterns of the most comprehensive list to date of housekeeping genes during iPS reprogramming of a mouse neural stem cell line N31. Our results show that housekeeping genes’ expression fuctuates signifcantly during the iPS reprogramming. Clustering analysis shows that ribosomal genes’ expression is rising, while the expression of cell-specifc genes, such as vimentin (Vim) or elastin (Eln), is decreasing. To ensure the robustness of the obtained data, we performed a correlative analysis of the genes. Overall, all 70 genes analyzed changed the expression more than two-fold during the reprogramming. The scale of this analysis, that takes into account 70 previously known and newly suggested genes, allowed us to choose the most stable of all genes. We highlight the fact of fuctuation of housekeeping genes during iPS reprogramming, and propose that, to ensure robustness of qPCR experiments in iPS cells, housekeeping genes should be used together in combination, and with a prior testing in a specifc line used in each study. We suggest that the longest splice variants of Rpl13a, Rplp1 and Rps18 can be used as a starting point for such initial testing as the most stable candidates. -
Centromere RNA Is a Key Component for the Assembly of Nucleoproteins at the Nucleolus and Centromere
Downloaded from genome.cshlp.org on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press Letter Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere Lee H. Wong,1,3 Kate H. Brettingham-Moore,1 Lyn Chan,1 Julie M. Quach,1 Melisssa A. Anderson,1 Emma L. Northrop,1 Ross Hannan,2 Richard Saffery,1 Margaret L. Shaw,1 Evan Williams,1 and K.H. Andy Choo1 1Chromosome and Chromatin Research Laboratory, Murdoch Childrens Research Institute & Department of Paediatrics, University of Melbourne, Royal Children’s Hospital, Parkville 3052, Victoria, Australia; 2Peter MacCallum Research Institute, St. Andrew’s Place, East Melbourne, Victoria 3002, Australia The centromere is a complex structure, the components and assembly pathway of which remain inadequately defined. Here, we demonstrate that centromeric ␣-satellite RNA and proteins CENPC1 and INCENP accumulate in the human interphase nucleolus in an RNA polymerase I–dependent manner. The nucleolar targeting of CENPC1 and INCENP requires ␣-satellite RNA, as evident from the delocalization of both proteins from the nucleolus in RNase-treated cells, and the nucleolar relocalization of these proteins following ␣-satellite RNA replenishment in these cells. Using protein truncation and in vitro mutagenesis, we have identified the nucleolar localization sequences on CENPC1 and INCENP. We present evidence that CENPC1 is an RNA-associating protein that binds ␣-satellite RNA by an in vitro binding assay. Using chromatin immunoprecipitation, RNase treatment, and “RNA replenishment” experiments, we show that ␣-satellite RNA is a key component in the assembly of CENPC1, INCENP, and survivin (an INCENP-interacting protein) at the metaphase centromere. -
Double Mitotic Nondisjunction
J Med Genet: first published as 10.1136/jmg.15.5.395 on 1 October 1978. Downloaded from Case reports 395 well be that, in this family, 18q- is unable to segre- mosaicism. Chromosome 18 trisomy was found gate properly during gametogenesis and early post- only in 18% of lymphocytes and not in skin zygotic mitosis, leading to an unbalanced state and fibroblasts. A likely interpretation is double non- +(18q-). disjunction in a single lymphocyte precursor HAROLD N. BASs, FELICE WEBER-PARISI, AND of a trisomy 21 embryo. A brief review of other ROBERT S. SPARKES cases of mitotic multiple nondisjunction and Department ofPediatrics (Genetics), Kaiser- double aneuploid mosaicism is presented. Permanente Medical Center, Panorama City, California 91402; and Division ofMedical Genetics, Chromosomal mosaicism occurs in a small percentage Departments ofMedicine, Pediatrics, andPsychiatry, of patients with Down's syndrome. The vast majority UCLA Centerfor the Health Sciences, Los Angeles, of these mosaics have a normal cell line in addition to California 90024, USA the trisomy 21 cell line. This report describes the first reported instance, to our knowledge, of an unusual References type of double trisomy mosaicism in lymphocytes Castel, Y., Riviere, D., Nawrocki, T., Le Fur, J-M., and Toudic, involving chromosomes 18 and 21. L. (1975). Trisomie partielie 18q par translocation familiale t(l8q-;13q+). Lyon Medical, 233, 211-217. Francke, U. (1972). Quinacrine mustard fluorescence of human chromosomes: characterization of unusual translocations. Case report American Journal ofHuman Genetics, 24, 189-213. Fujita, K., and Fujita, H. M. (1974). An extra small submetacentric The proposita was referred for chromosome analysis chromosome: possible partial trisomy 18. -
Review Article PTEN Gene: a Model for Genetic Diseases in Dermatology
The Scientific World Journal Volume 2012, Article ID 252457, 8 pages The cientificWorldJOURNAL doi:10.1100/2012/252457 Review Article PTEN Gene: A Model for Genetic Diseases in Dermatology Corrado Romano1 and Carmelo Schepis2 1 Unit of Pediatrics and Medical Genetics, I.R.C.C.S. Associazione Oasi Maria Santissima, 94018 Troina, Italy 2 Unit of Dermatology, I.R.C.C.S. Associazione Oasi Maria Santissima, 94018 Troina, Italy Correspondence should be addressed to Carmelo Schepis, [email protected] Received 19 October 2011; Accepted 4 January 2012 Academic Editors: G. Vecchio and H. Zitzelsberger Copyright © 2012 C. Romano and C. Schepis. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan- Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. -
Epigenetic Centromere Specification Directs Aurora B Accumulation but Is Insufficient to Efficiently Correct Mitotic Errors
JCB: Report Epigenetic centromere specification directs aurora B accumulation but is insufficient to efficiently correct mitotic errors Emily A. Bassett,1,2 Stacey Wood,2 Kevan J. Salimian,1,2 Sandya Ajith,1,2 Daniel R. Foltz,3 and Ben E. Black1,2 1Graduate Group in Biochemistry and Molecular Biophysics and 2Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 3Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908 he nearly ubiquitous presence of repetitive centro- of the kinetochore is intact at a human neocentromere mere DNA sequences across eukaryotic species is in lacking repetitive -satellite DNA. However, aurora B is Tparadoxical contrast to their apparent functional dis- inappropriately silenced as a consequence of the altered pensability. Centromeric chromatin is spatially delineated geometry of the neocentromere, thereby compromising into the kinetochore-forming array of centromere protein A the error correction mechanism. This suggests a model (CENP-A)–containing nucleosomes and the inner cen wherein the neocentromere represents a primordial inher- tromeric heterochromatin that lacks CENP-A but recruits itance locus that requires subsequent generation of a the aurora B kinase that is necessary for correcting erro- robust inner centromere compartment to enhance fidelity neous attachments to the mitotic spindle. We found that of chromosome transmission. the self-perpetuating network of CENPs at the foundation Introduction -
Questions from Medical Biology and Genetics in Acad. Year 2019/2020 for 1 St Year Dentistry
Questions from Medical biology and Genetics in acad. year 2019/2020 for 1 st year Dentistry I. The cell 1. Molecular structure of the biological membranes 2. Types of intercellular communications (endocrine, paracrine, autocrine and neural) 3. Types and function of receptors and signal molecules, first and second messengers, amplification of signal 4. Transport through membranes, mechanisms 5. Endoplasmic reticulum, structure and function 6. Ribosomes, their structure and function 7. Golgi complex, its structure, metabolic and distributional function 8. Lysosomes, peroxisomes, proteasomes and their function 9. Function and biogenesis mitochondria, characteristics of its genome 10. Functional organization of the cytoskeleton (microtubules, microfillaments) 11. Centromere, kinetochore, system permitting movement of chromosomes in cell division 12. Mitosis as a part of cell cycle 13. Cell cycle - phases, regulatory molecules, check points 14. Processes taking part in cell cycle regulation, examples 15. G1 check point of cell cycle, factors ruling transfer G1/S in cell cycle 16. G2 check point of cell cycle, factors ruling transfer G2/M in cell cycle 17. Mitotic check point, molecular mechanism of its regulation 18. Relation protooncogene – oncogene in regulation of cell cycle 19. Oncogenesis, molecular characteristics of malignant transformation of cell 20. Types of oncogenes, mechanisms changing protooncogene to oncogene 21. Mechanisms of protooncogens participation in deregulation of cell cycle 22. Nucleus, its structure and function 23. Totipotence of cells, stem cells, tissue engineering and regenerative medicine 24. Alternative usage of genetic information in differentiation of cell 25. Apoptosis - programmed cell death (telomeric sequences) 26. Mechanism of activation of apoptosis through ”death“ receptors 27. Mechanism of activation of apoptosis through mitochondrial pathway 28. -
Sample Thesis Title with a Concise and Accurate
DISTINCT FUNCTIONS FOR THE HIGHLY RELATED PP2A B55 REGULATORY SUBUNITS (Bα AND Bδ) IN CELL CYCLE REGULATION AND TUMOURIGENESIS by Dominik Sommerfeld B.Sc., The University of British Columbia, 2009 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2018 © Dominik Sommerfeld, 2018 The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Distinct functions for the highly related PP2A B55 regulatory subunits (Bα and Bδ) in cell cycle regulation and tumourigenesis submitted by Dominik Sommerfeld in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee: Catherine Pallen, Ph.D. Supervisor Christopher Maxwell, Ph.D. Supervisory Committee Member Gregg Morin, Ph.D. Supervisory Committee Member Stephan Taubert, Ph.D. University Examiner Calvin Roskelley, Ph.D. University Examiner Additional Supervisory Committee Members: Samuel Aparicio, Ph.D. Supervisory Committee Member ii Abstract Progression through the phases of the cell cycle (G1, S, G2, and mitosis) is largely driven by the coordinated activities of protein kinases and phosphatases, which orchestrate the phase-specific phosphorylation of proteins. Protein Phosphatase 2A (PP2A) – a heterotrimeric holoenzyme complex composed of a scaffold (A), catalytic (C), and variable regulatory (B) subunit – has emerged as an essential cell cycle regulator. Specifically, PP2A complexes containing the B55 family of regulatory subunits (PP2A-B55) have been implicated in the control of various cell cycle phases. My studies investigated isoform-specific roles of the two highly related and abundantly expressed B55 subunits, Bα and Bδ, in the regulation of G1, S, G2 phase and mitotic progression. -
Phosphorylation of Threonine 3 on Histone H3 by Haspin Kinase Is Required for Meiosis I in Mouse Oocytes
ß 2014. Published by The Company of Biologists Ltd | Journal of Cell Science (2014) 127, 5066–5078 doi:10.1242/jcs.158840 RESEARCH ARTICLE Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes Alexandra L. Nguyen, Amanda S. Gentilello, Ahmed Z. Balboula*, Vibha Shrivastava, Jacob Ohring and Karen Schindler` ABSTRACT a lesser extent. However, it is not known whether haspin is required for meiosis in oocytes. To date, the only known haspin substrates Meiosis I (MI), the division that generates haploids, is prone to are threonine 3 of histone H3 (H3T3), serine 137 of macroH2A and errors that lead to aneuploidy in females. Haspin is a kinase that threonine 57 of CENP-T (Maiolica et al., 2014). Knockdown or phosphorylates histone H3 on threonine 3, thereby recruiting Aurora inhibition of haspin in mitotically dividing tissue culture cell kinase B (AURKB) and the chromosomal passenger complex lines reveal that phosphorylation of H3T3 is essential for the (CPC) to kinetochores to regulate mitosis. Haspin and AURKC, an alignment of chromosomes at the metaphase plate (Dai and AURKB homolog, are enriched in germ cells, yet their significance Higgins, 2005; Dai et al., 2005), regulation of chromosome in regulating MI is not fully understood. Using inhibitors and cohesion (Dai et al., 2009) and establishing a bipolar spindle (Dai overexpression approaches, we show a role for haspin during MI et al., 2009). In mitotic metaphase, phosphorylation of H3T3 is in mouse oocytes. Haspin-perturbed oocytes display abnormalities restricted to kinetochores, and this mark signals recruitment of the in chromosome morphology and alignment, improper kinetochore– chromosomal passenger complex (CPC) (Dai et al., 2005; Wang microtubule attachments at metaphase I and aneuploidy at et al., 2010; Yamagishi et al., 2010). -
A Single Amino Acid Change Converts Aurora-A Into Aurora-B-Like Kinase in Terms of Partner Specificity and Cellular Function
A single amino acid change converts Aurora-A into Aurora-B-like kinase in terms of partner specificity and cellular function Jingyan Fua, Minglei Biana, Junjun Liub, Qing Jianga, and Chuanmao Zhanga,1 aThe Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, College of Life Sciences, Peking University, Beijing 100871, China; and bDepartment of Biological Sciences, California State Polytechnic University, Pomona, CA 91768 Edited by Don W. Cleveland, University of California at San Diego, La Jolla, CA, and approved March 5, 2009 (received for review January 25, 2009) Aurora kinase-A and -B are key regulators of the cell cycle and the original Aurora-A localization at the spindle. Moreover, tumorigenesis. It has remained a mystery why these 2 Aurora Aurora-AG198N prevented the chromosome misalignment and kinases, although highly similar in protein sequence and structure, cell premature exit from mitosis caused by Aurora-B knock- are distinct in subcellular localization and function. Here, we report down, indicating functional substitution for Aurora-B in cell the striking finding that a single amino acid residue is responsible cycle regulation. for these differences. We replaced the Gly-198 of Aurora-A with the equivalent residue Asn-142 of Aurora-B and found that in HeLa Results cells, Aurora-AG198N was recruited to the inner centromere in Aurora-AG198N Colocalizes with Aurora-B at Centromere and Midzone. metaphase and the midzone in anaphase, reminiscent of the We fused the mutants Aurora-AG198N and Aurora-BN142G (Fig. Aurora-B localization. Moreover, Aurora-AG198N compensated for 1A) with GFP and transiently expressed them in HeLa cells the loss of Aurora-B in chromosome misalignment and cell prema- [supporting information (SI) Fig.