A Acentric Fragment Linear One Telomere Radiation One Broken End Endonuclease Break-Inducing Mutagen
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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. -
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. -
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. -
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. -
The Recognition and Mobility of DNA Double-Strand Breaks
The Recognition and Mobility of DNA Double-Strand Breaks by Jonathan Strecker A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Molecular Genetics University of Toronto © Copyright by Jonathan Strecker 2016 The Recognition and Mobility of DNA Double-Strand Breaks Jonathan Strecker Doctor of Philosophy Graduate Department of Molecular Genetics University of Toronto 2016 Abstract DNA double-strand breaks (DSBs) pose a threat to cell survival and genomic integrity, and remarkable mechanisms exist to deal with these breaks. A single DSB activates a signalling response that profoundly impacts cell physiology, not least through the engagement of DSB repair pathways and the arrest of cell division. Here I study these processes in the budding yeast Saccharomyces cerevisiae and investigate two central themes to this response. First, I examine how the natural ends of chromosomes, telomeres, are differentiated from DSBs by generating DNA ends with increasing telomeric character. I discover a striking transition in the activity of the telomerase inhibitor Pif1 at these ends and propose that this is the dividing line between DSBs and telomeres. Second, I investigate a phenomenon whereby a DSB increases the mobility of chromosomes within the nucleus. This increase in mobility is dependent on the Mec1 kinase and is proposed to promote repair by homologous recombination. I identify that the Mec1-dependent phosphorylation of Cep3, a kinetochore component, is required to stimulate chromatin mobility following DNA breakage and provide a new model for how a DSB affects the constraints on chromosomes. Unexpectedly, I find that increased mobility is not required for DSB repair and instead propose that Cep3 helps arrest the cell cycle in response to a DSB. -
Atypical Centromeres in Plants—What They Can Tell Us Cuacos, Maria; H
University of Birmingham Atypical centromeres in plants—what they can tell us Cuacos, Maria; H. Franklin, F. Chris; Heckmann, Stefan DOI: 10.3389/fpls.2015.00913 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Cuacos, M, H. Franklin, FC & Heckmann, S 2015, 'Atypical centromeres in plants—what they can tell us', Frontiers in Plant Science, vol. 6, 913. https://doi.org/10.3389/fpls.2015.00913 Link to publication on Research at Birmingham portal Publisher Rights Statement: Eligibility for repository : checked 18/11/2015 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive. -
Haplotype-Aware Inference of Human Chromosome Abnormalities Daniel Ariad 1*, Stephanie M
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.18.444721; this version posted May 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Ariad et al. Haplotype-aware inference of human chromosome abnormalities Daniel Ariad 1*, Stephanie M. Yan 1, Andrea R. Victor2,FrankL.Barnes2, Christo G. Zouves2, Manuel Viotti 3 and Rajiv C. McCoy 1* Abstract Extra or missing chromosomes—a phenomenon termed aneuploidy—frequently arises during human meiosis and embryonic mitosis and is the leading cause of pregnancy loss, including in the context of in vitro fertilization (IVF). While meiotic aneuploidies a↵ect all cells and are deleterious, mitotic errors generate mosaicism, which may be compatible with healthy live birth. Large-scale abnormalities such as triploidy and haploidy also contribute to adverse pregnancy outcomes, but remain hidden from standard sequencing-based approaches to preimplantation genetic testing (PGT-A). The ability to reliably distinguish meiotic and mitotic aneuploidies, as well as abnormalities in genome-wide ploidy may thus prove valuable for enhancing IVF outcomes. Here, we describe a statistical method for distinguishing these forms of aneuploidy based on analysis of low-coverage whole-genome sequencing data, which is the current standard in the field. Our approach overcomes the sparse nature of the data by leveraging allele frequencies and linkage disequilibrium (LD) measured in a population reference panel. The method, which we term LD-informed PGT-A (LD-PGTA), retains high accuracy down to coverage as low as 0.05 and at higher coverage can also distinguish between meiosis I and meiosis II errors based on signatures⇥ spanning the centromeres. -
Large-Scale Chromosomal Changes 1
Large-Scale Chromosomal Changes 1. MM N OO would be classified as 2n–1; MM NN OO would be classified as 2n; and MMM NN PP would be classified as 2n+1. 2. It would more likely be an autopolyploid. To make sure it was polyploid, you would need to microscopically examine stained chromosomes from mitotically dividing cells and count the chromosome number. 3. Aneuploid. Trisomic refers to three copies of one chromosome. Triploid refers to three copies of all chromosomes. 5. No. Amphidiploid means “doubled diploid.” Because cauliflower has n = 9 chromosome, it could not have arose in this fashion. It has, however, contributed to other amphidiploid species. 9. Cells destined to become pollen grains can be induced by cold treatment to grow into embryoids. These embryoids can then be grown on agar to form monoploid plantlets. 11. Yes. You would expect that one-sixth of the gametes would be a. Also, two-sixths would be A, two-sixths would be Aa, and one-sixth would be AA. 12. Both XXY and XXX would be fertile. XO (Turner) and XXY (Klinefelter) are both sterile. 13. Older mothers have an elevated risk of having a child with Down syndrome and other non-disjunctional events. 14. No. The DNA backbone has strict 5´ to 3´ polarity, and 5´ ends can only be joined to 3´ ends. 15. A crossover within a paracentric inversion heterozygote results in a dicentric bridge (and an acentric fragment). 16. An acentric fragment cannot be aligned or moved during meiosis (or mitosis) and consequently is lost. 20. -
The Force for Poleward Chromosome Motion in Haemanthus Cells Acts
The Force for Poleward Chromosome Motion in Haemanthus Cells Acts along the Length of the Chromosome during Metaphase but Only at the Kinetochore during Anaphase Alexey Khodjakov,* Richard W. Cole,* Andrew S. Bajer, ~ and Conly L. Rieder** *Laboratory of Cell Regulation, Wadsworth Center for Laboratories and Research, Albany, New York 12201-0509; ~Department of Biomedical Sciences, State University of New York, Albany, New York 12222; and§Department of Biology, University of Oregon, Eugene, Oregon 97403 Abstract. The force for poleward chromosome motion other force that now transported the fragments to the during mitosis is thought to act, in all higher organisms, spindle equator at 1.5-2.0 tzm/min. These fragments exclusively through the kinetochore. We have used then remained near the spindle midzone until phrag- time-lapse, video-enhanced, differential interference moplast development, at which time they were again contrast light microscopy to determine the behavior of transported randomly poleward but now at ~3/xm/min. kinetochore-free "acentric" chromosome fragments This behavior of acentric chromosome fragments on and "monocentric" chromosomes containing one kine- anastral plant spindles differs from that reported for tochore, created at various stages of mitosis in living the astral spindles of vertebrate cells, and demonstrates higher plant (Haemanthus) cells by laser microsurgery. that in forming plant spindles, a force for poleward Acentric fragments and monocentric chromosomes chromosome motion is generated independent of the generated during spindle formation and metaphase kinetochore. The data further suggest that the three both moved towards the closest spindle pole at a rate stages of non-kinetochore chromosome transport we (~1.0 txm/min) similar to the poleward motion of observed are all mediated by the spindle microtubules. -
Genome-Wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells
Journal of Visualized Experiments www.jove.com Video Article Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells Henrik D. Møller1, Rasmus K. Bojsen2, Chris Tachibana3, Lance Parsons4, David Botstein5, Birgitte Regenberg1 1 Department of Biology, University of Copenhagen 2 National Veterinary Institute, Technical University of Denmark 3 Group Health Research Institute 4 Lewis-Sigler Institute for Integrative Genomics, Princeton University 5 Calico Life Sciences LLC Correspondence to: Birgitte Regenberg at [email protected] URL: https://www.jove.com/video/54239 DOI: doi:10.3791/54239 Keywords: Molecular Biology, Issue 110, Circle-Seq, deletion, eccDNA, rDNA, ERC, ECE, microDNA, minichromosomes, small polydispersed circular DNA, spcDNA, double minute, amplification Date Published: 4/4/2016 Citation: Møller, H.D., Bojsen, R.K., Tachibana, C., Parsons, L., Botstein, D., Regenberg, B. Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells. J. Vis. Exp. (110), e54239, doi:10.3791/54239 (2016). Abstract Extrachromosomal circular DNAs (eccDNAs) are common genetic elements in Saccharomyces cerevisiae and are reported in other eukaryotes as well. EccDNAs contribute to genetic variation among somatic cells in multicellular organisms and to evolution of unicellular eukaryotes. Sensitive methods for detecting eccDNA are needed to clarify how these elements affect genome stability and how environmental and biological factors induce their formation in eukaryotic cells. This video presents a sensitive eccDNA-purification method called Circle-Seq. The method encompasses column purification of circular DNA, removal of remaining linear chromosomal DNA, rolling-circle amplification of eccDNA, deep sequencing, and mapping. Extensive exonuclease treatment was required for sufficient linear chromosomal DNA degradation. The rolling-circle amplification step by φ29 polymerase enriched for circular DNA over linear DNA. -
Double Minute Chromosomes in Glioblastoma Multiforme Are Revealed by Precise Reconstruction of Oncogenic Amplicons
Published OnlineFirst August 12, 2013; DOI: 10.1158/0008-5472.CAN-13-0186 Cancer Tumor and Stem Cell Biology Research Double Minute Chromosomes in Glioblastoma Multiforme Are Revealed by Precise Reconstruction of Oncogenic Amplicons J. Zachary Sanborn1,2,Sofie R. Salama2,3, Mia Grifford2, Cameron W. Brennan4, Tom Mikkelsen6, Suresh Jhanwar5, Sol Katzman2, Lynda Chin7, and David Haussler2,3 Abstract DNA sequencing offers a powerful tool in oncology based on the precise definition of structural rearrange- ments and copy number in tumor genomes. Here, we describe the development of methods to compute copy number and detect structural variants to locally reconstruct highly rearranged regions of the tumor genome with high precision from standard, short-read, paired-end sequencing datasets. We find that circular assemblies are the most parsimonious explanation for a set of highly amplified tumor regions in a subset of glioblastoma multiforme samples sequenced by The Cancer Genome Atlas (TCGA) consortium, revealing evidence for double minute chromosomes in these tumors. Further, we find that some samples harbor multiple circular amplicons and, in some cases, further rearrangements occurred after the initial amplicon-generating event. Fluorescence in situ hybridization analysis offered an initial confirmation of the presence of double minute chromosomes. Gene content in these assemblies helps identify likely driver oncogenes for these amplicons. RNA-seq data available for one double minute chromosome offered additional support for our local tumor genome assemblies, and identified the birth of a novel exon made possible through rearranged sequences present in the double minute chromosomes. Our method was also useful for analysis of a larger set of glioblastoma multiforme tumors for which exome sequencing data are available, finding evidence for oncogenic double minute chromosomes in more than 20% of clinical specimens examined, a frequency consistent with previous estimates.