DOCSLIB.ORG

Environmental Protection Agency § 799.9537

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Environmental Protection Agency § 799.9537 Environmental Protection Agency § 799.9537 Lymphoma Mutagen Assay System. ¥ 3.7.2C Mouse Lymphoma Cells. Mutation Reseach. 59, 61–108 (1979). Mutagenesis. 5, 609–614 (1990). (17) Maron, D.M. and Ames, B.N. Re- vised Methods for the Salmonella Mu- [62 FR 43824, Aug. 15, 1997, as amended at 77 FR 46294, Aug. 3, 2012] tagenicity Test. Mutation Reseach. 113, 173, 215 (1983). § 799.9537 TSCA in vitro mammalian (18) Elliott, B.M., Combes, R.D., chromosome aberration test. Elcombe, C.R., Gatehouse, D.G., Gib- son, G.G., Mackay, J.M., and Wolf, R.C. (a) Scope—(1) Applicability. This sec- Alternatives to Aroclor 1254-Induced S9 tion is intended to meet testing re- in In Vitro Genotoxicity Assays. quirements under section 4 of the Toxic Mutagenesis. 7, 175–177 (1992). Substances Control Act (TSCA) (15 (19) Matsushima, T., Sawamura, M., U.S.C. 2601). Hara, K., and Sugimura, T. A Safe Sub- (2) Background. The source material stitute for Polychlorinated Biphenyls used in developing this TSCA test as an Inducer of Metabolic Activation guideline is the Office of Prevention, Systems. (Eds.) de Serres, F.J., Fouts, Pesticides, and Toxic Substances J.R., Bend, J.R., and Philpot, R.M. In (OPPTS) harmonized test guideline Vitro Metabolic Activation in Mutagenesis 870.5375 (August 1998, final guidelines). Testing (Elsevier, North-Holland, 1976) The source is available at the address pp. 85–88. in paragraph (i) of this section. (20) Krahn, D.F., Barsky, F.C., and (b) Purpose. (1) The purpose of the in McCooey, K.T. Eds. Tice, R.R., Costa, vitro chromosome aberration test is to D.L., and Schaich, K.M. CHO/HGPRT identify agents that cause structural Mutation Assay: Evaluation of Gases chromosome aberrations in cultured and Volatile Liquids. Genotoxic Effects mammalian cells (see paragraphs (i)(1), of Airborne Agents (New York, Plenum, (i)(2), and (i)(3) of this section). Struc- 1982) pp. 91–103. tural aberrations may be of two types, (21) Zamora, P.O., Benson, J.M., Li, chromosome or chromatid. With the A.P., and Brooks, A.L. Evaluation of an majority of chemical mutagens, in- Exposure System Using Cells Grown on duced aberrations are of the chromatid Collagen Gels for Detecting Highly type, but chromosome-type aberrations Volatile Mutagens in the CHO/HGPRT also occur. An increase in polyploidy Mutation Assay. Environmental may indicate that a chemical has the Mutagenesis. 5, 795–801 (1983). potential to induce numerical aberra- (22) Applegate, M.L., Moore, M.M., tions. However, this guideline is not Broder, C.B., Burrell, A., and Hozier, designed to measure numerical aberra- J.C. Molecular Dissection of Mutations tions and is not routinely used for that at the Heterozygous Thymidine Kinase purpose. Chromosome mutations and Locus in Mouse Lymphoma Cells. Proc. related events are the cause of many National Academy Science (USA, 1990) human genetic diseases and there is 87, 51–55. substantial evidence that chromosome (23) Moore, M.M., Clive, D., Hozier, mutations and related events causing J.C., Howard, B.E., Batson, A.G., Tur- alterations in oncogenes and tumour- ner, N.T., and Sawyer, J. Analysis of suppressor genes of somatic cells are Trifluorothymidine-Resistant (TFTr) involved in cancer induction in humans = Mutants of L5178Y/TK /¥ Mouse and experimental animals. Lymphoma Cells. Mutation Research. (2) The in vitro chromosome aberra- 151, 161–174 (1985). tion test may employ cultures of estab- (24) Yandell, D.W., Dryja, T.P., and lished cell lines, cell strains or primary Little J.B. Molecular Genetic Analysis cell cultures. The cells used are se- of Recessive Mutations at a lected on the basis of growth ability in Heterozygous Autosomal Locus in culture, stability of the karyotype, Human Cells. Mutation Research. 229, chromosome number, chromosome di- 89–102 (1990). versity, and spontaneous frequency of (25) Moore, M.M. and Doerr, C.L. chromosome aberrations. Comparison of Chromosome Aberration (c) Definitions. The definitions in sec- Frequency and Small-Colony TK-Defi- tion 3 of TSCA and in 40 CFR Part 792— cient Mutant Frequency in L5178Y/TK=/ Good Laboratory Practice Standards 445 VerDate Mar<15>2010 14:29 Jul 26, 2013 Jkt 229179 PO 00000 Frm 00455 Fmt 8010 Sfmt 8010 Y:\SGML\229179.XXX 229179 ehiers on DSK2VPTVN1PROD with CFR § 799.9537 40 CFR Ch. I (7–1–13 Edition) apply to this test guideline. The fol- positive in this test are mammalian lowing definitions also apply to this carcinogens; however, there is not a test guideline. perfect correlation between this test Chromatid-type aberration is struc- and carcinogenicity. Correlation is de- tural chromosome damage expressed as pendent on chemical class and there is breakage of single chromatids or increasing evidence that there are car- breakage and reunion between cinogens that are not detected by this chromatids. test because they appear to act Chromosome-type aberration is struc- through mechanisms other than direct tural chromosome damage expressed as DNA damage. breakage, or breakage and reunion, of (e) Principle of the test method. Cell both chromatids at an identical site. cultures are exposed to the test sub- Endoreduplication is a process in stance both with and without meta- which after an S period of DNA replica- bolic activation. At predetermined in- tion, the nucleus does not go into mito- tervals after exposure of cell cultures sis but starts another S period. The re- to the test substance, they are treated sult is chromosomes with 4, 8, with a metaphase-arresting substance 16,...chromatids. (e.g., Colcemid ® or colchicine), har- Gap is an achromatic lesion smaller vested, stained, and metaphase cells than the width of one chromatid, and are analysed microscopically for the with minimum misalignment of the presence of chromosome aberrations. chromatid(s). (f) Description of the method—(1) Prep- Mitotic index is the ratio of cells in arations—(i) Cells. A variety of cell metaphase divided by the total number lines, strains, or primary cell cultures, of cells observed in a population of including human cells, may be used cells; an indication of the degree of (e.g., Chinese hamster fibroblasts, proliferation of that population. human, or other mammalian peripheral Numerical aberration is a change in blood lymphocytes). the number of chromosomes from the (ii) Media and culture conditions. Ap- normal number characteristic of the propriate culture media, and incuba- cells utilized. tion conditions (culture vessels, CO2 Polyploidy is a multiple of the concentration, temperature and humid- haploid chromosome number (n) other ity) must be used in maintaining cul- than the diploid number (i.e., 3n, 4n, tures. Established cell lines and strains and so on). must be checked routinely for stability Structural aberration is a change in in the modal chromosome number and chromosome structure detectable by the absence of Mycoplasma contamina- microscopic examination of the meta- tion and should not be used if contami- phase stage of cell division, observed as nated. The normal cell-cycle time for deletions and fragments, intrachanges, the cells and culture conditions used and interchanges. should be known. (d) Initial considerations. (1) Tests con- (iii) Preparation of cultures—(A) Estab- ducted in vitro generally require the lished cell lines and strains. Cells are use of an exogenous source of meta- propagated from stock cultures, seeded bolic activation. This metabolic acti- in culture medium at a density such vation system cannot mimic entirely that the cultures will not reach the mammalian in vivo conditions. confluency before the time of harvest, Care should be taken to avoid condi- and incubated at 37 °C. tions which would lead to positive re- (B) Lymphocytes. Whole blood treated sults which do not reflect intrinsic mu- with an anti-coagulant (e.g., heparin) tagenicity and may arise from changes or separated lymphocytes obtained in pH, osmolality, or high levels of from healthy subjects are added to cul- cytotoxicity (the test techniques de- ture medium containing a mitogen scribed in the references under para- (e.g., phytohemagglutinin) and incu- graphs (i)(4) and (i)(5) of this section bated at 37 °C. may be used). (iv) Metabolic activation. Cells must (2) This test is used to screen for pos- be exposed to the test substance both sible mammalian mutagens and car- in the presence and absence of an ap- cinogens. Many compounds that are propriate metabolic activation system. 446 VerDate Mar<15>2010 14:29 Jul 26, 2013 Jkt 229179 PO 00000 Frm 00456 Fmt 8010 Sfmt 8010 Y:\SGML\229179.XXX 229179 ehiers on DSK2VPTVN1PROD with CFR Environmental Protection Agency § 799.9537 The most commonly used system is a (ii) Exposure concentrations. (A) co-factor-supplemented post- Among the criteria to be considered mitochondrial fraction (S9) prepared when determining the highest con- from the livers of rodents treated with centration are cytotoxicity, solubility enzyme-inducing agents such as in the test system, and changes in pH Aroclor 1254 (the test techniques de- or osmolality. scribed in the references under para- (B) Cytotoxicity should be deter- graphs (i)(6), (i)(7), (8)(i), and (i)(9) of mined with and without metabolic ac- this section may be used), or a mixture tivation in the main experiment using of phenobarbitone and b- an appropriate indication of cell integ- naphthoflavone (the test techniques de- rity and growth, such as degree of scribed in the references under para- confluency, viable cell counts, or mi- graphs (i)(10), (i)(11), and (i)(12) of this totic index. It may be useful to deter- section may be used). The post- mine cytotoxicity and solubility in a mitochondrial fraction is usually used preliminary experiment. at concentrations in the range from 1- (C) At least three analyzable con- 10% v/v in the final test medium.
Load more

Recommended publications
  • Chromatid Cohesion During Mitosis: Lessons from Meiosis
    Journal of Cell Science 112, 2607-2613 (1999) 2607 Printed in Great Britain © The Company of Biologists Limited 1999 JCS0467 COMMENTARY Chromatid cohesion during mitosis: lessons from meiosis Conly L. Rieder1,2,3 and Richard Cole1 1Wadsworth Center, New York State Dept of Health, PO Box 509, Albany, New York 12201-0509, USA 2Department of Biomedical Sciences, State University of New York, Albany, New York 12222, USA 3Marine Biology Laboratory, Woods Hole, MA 02543-1015, USA *Author for correspondence (e-mail: [email protected]) Published on WWW 21 July 1999 SUMMARY The equal distribution of chromosomes during mitosis and temporally separated under various conditions. Finally, we meiosis is dependent on the maintenance of sister demonstrate that in the absence of a centromeric tether, chromatid cohesion. In this commentary we review the arm cohesion is sufficient to maintain chromatid cohesion evidence that, during meiosis, the mechanism underlying during prometaphase of mitosis. This finding provides a the cohesion of chromatids along their arms is different straightforward explanation for why mutants in proteins from that responsible for cohesion in the centromere responsible for centromeric cohesion in Drosophila (e.g. region. We then argue that the chromatids on a mitotic ord, mei-s332) disrupt meiosis but not mitosis. chromosome are also tethered along their arms and in the centromere by different mechanisms, and that the Key words: Sister-chromatid cohesion, Mitosis, Meiosis, Anaphase functional action of these two mechanisms can be onset INTRODUCTION (related to the fission yeast Cut1P; Ciosk et al., 1998). When Pds1 is destroyed Esp1 is liberated, and this event somehow The equal distribution of chromosomes during mitosis is induces a class of ‘glue’ proteins, called cohesins (e.g.
    [Show full text]
  • Mitosis Vs. Meiosis
    Mitosis vs. Meiosis In order for organisms to continue growing and/or replace cells that are dead or beyond repair, cells must replicate, or make identical copies of themselves. In order to do this and maintain the proper number of chromosomes, the cells of eukaryotes must undergo mitosis to divide up their DNA. The dividing of the DNA ensures that both the “old” cell (parent cell) and the “new” cells (daughter cells) have the same genetic makeup and both will be diploid, or containing the same number of chromosomes as the parent cell. For reproduction of an organism to occur, the original parent cell will undergo Meiosis to create 4 new daughter cells with a slightly different genetic makeup in order to ensure genetic diversity when fertilization occurs. The four daughter cells will be haploid, or containing half the number of chromosomes as the parent cell. The difference between the two processes is that mitosis occurs in non-reproductive cells, or somatic cells, and meiosis occurs in the cells that participate in sexual reproduction, or germ cells. The Somatic Cell Cycle (Mitosis) The somatic cell cycle consists of 3 phases: interphase, m phase, and cytokinesis. 1. Interphase: Interphase is considered the non-dividing phase of the cell cycle. It is not a part of the actual process of mitosis, but it readies the cell for mitosis. It is made up of 3 sub-phases: • G1 Phase: In G1, the cell is growing. In most organisms, the majority of the cell’s life span is spent in G1. • S Phase: In each human somatic cell, there are 23 pairs of chromosomes; one chromosome comes from the mother and one comes from the father.
    [Show full text]
  • Aging Mice Have Increased Chromosome Instability That Is Exacerbated by Elevated Mdm2 Expression
    Oncogene (2011) 30, 4622–4631 & 2011 Macmillan Publishers Limited All rights reserved 0950-9232/11 www.nature.com/onc ORIGINAL ARTICLE Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression T Lushnikova1, A Bouska2, J Odvody1, WD Dupont3 and CM Eischen1 1Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA and 3Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA Aging is thought to negatively affect multiple cellular Introduction processes including the ability to maintain chromosome stability. Chromosome instability (CIN) is a common Genomic instability refers to the accumulation or property of cancer cells and may be a contributing factor acquisition of numerical and/or structural abnormali- to cellular transformation. The types of DNA aberrations ties in chromosomes. It has long been observed that that arise during aging before tumor development and that chromosome instability (CIN) is a hallmark of cancer contribute to tumorigenesis are currently unclear. Mdm2, cells and is postulated to be required for tumorigenesis a key regulator of the p53 tumor suppressor and (Lengauer et al., 1998; Negrini et al., 2010). Genomic modulator of DNA break repair, is frequently over- changes, such as chromosome breaks, translocations, expressed in malignancies and contributes to CIN. To genome rearrangements, aneuploidy and telomere short- determine the relationship between aging and CIN and the ening have been observed in aging organisms (Nisitani role of Mdm2, precancerous wild-type C57Bl/6 and et al., 1990; Tucker et al., 1999; Dolle and Vijg, 2002; littermate-matched Mdm2 transgenic mice at various Aubert and Lansdorp, 2008; Zietkiewicz et al., 2009).
    [Show full text]
  • Anaphase Bridges: Not All Natural Fibers Are Healthy
    G C A T T A C G G C A T genes Review Anaphase Bridges: Not All Natural Fibers Are Healthy Alice Finardi 1, Lucia F. Massari 2 and Rosella Visintin 1,* 1 Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy; alice.fi[email protected] 2 The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK; [email protected] * Correspondence: [email protected]; Tel.: +39-02-5748-9859; Fax: +39-02-9437-5991 Received: 14 July 2020; Accepted: 5 August 2020; Published: 7 August 2020 Abstract: At each round of cell division, the DNA must be correctly duplicated and distributed between the two daughter cells to maintain genome identity. In order to achieve proper chromosome replication and segregation, sister chromatids must be recognized as such and kept together until their separation. This process of cohesion is mainly achieved through proteinaceous linkages of cohesin complexes, which are loaded on the sister chromatids as they are generated during S phase. Cohesion between sister chromatids must be fully removed at anaphase to allow chromosome segregation. Other (non-proteinaceous) sources of cohesion between sister chromatids consist of DNA linkages or sister chromatid intertwines. DNA linkages are a natural consequence of DNA replication, but must be timely resolved before chromosome segregation to avoid the arising of DNA lesions and genome instability, a hallmark of cancer development. As complete resolution of sister chromatid intertwines only occurs during chromosome segregation, it is not clear whether DNA linkages that persist in mitosis are simply an unwanted leftover or whether they have a functional role.
    [Show full text]
  • Pds5 Regulators Segregate Cohesion and Condensation Pathways in Saccharomyces Cerevisiae
    Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae Kevin Tong and Robert V. Skibbens1 Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015 Edited by Douglas Koshland, University of California, Berkeley, CA, and approved April 23, 2015 (received for review January 21, 2015) Cohesins are required both for the tethering together of sister these cohesion-related processes are so intimately entwined as to chromatids (termed cohesion) and subsequent condensation into be potentially inseparable. discrete structures—processes fundamental for faithful chromo- Cells from RBS patients typically exhibit heterochromatic re- some segregation into daughter cells. Differentiating between pulsion (regionalized condensation defects) absent in cells from cohesin roles in cohesion and condensation would provide an im- CdLS patients. The presence of aneuploidy and failed mitosis also portant advance in studying chromatin metabolism. Pds5 is a cohe- appears to differentiate, at the cellular level, otherwise highly sin-associated factor that is essential for both cohesion maintenance similar developmental abnormalities(12,20).Therefore,theidenti- and condensation. Recent studies revealed that ELG1 deletion sup- fication of pathways through which cohesion and condensation are presses the temperature sensitivity of pds5 mutant cells. However, experimentally separated would provide important tools useful in the mechanisms through which Elg1 may regulate cohesion and con- dissecting each pathway in isolation and provide a broader un- densation remain unknown. Here, we report that ELG1 deletion from derstanding of the multifaceted cohesin complex. A limited number pds5-1 mutant cells results in a significant rescue of cohesion, but not of genes (RAD61/WAPL and ELG1), when deleted, suppress condensation, defects. Based on evidence that Elg1 unloads the DNA ctf7/eco1 mutant cell growth deficiencies.
    [Show full text]
  • Repression of Harmful Meiotic Recombination in Centromeric Regions
    Seminars in Cell & Developmental Biology 54 (2016) 188–197 Contents lists available at ScienceDirect Seminars in Cell & Developmental Biology j ournal homepage: www.elsevier.com/locate/semcdb Review Repression of harmful meiotic recombination in centromeric regions ∗ Mridula Nambiar, Gerald R. Smith Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA, United States a r t i c l e i n f o a b s t r a c t Article history: During the first division of meiosis, segregation of homologous chromosomes reduces the chromosome Received 23 November 2015 number by half. In most species, sister chromatid cohesion and reciprocal recombination (crossing-over) Accepted 27 January 2016 between homologous chromosomes are essential to provide tension to signal proper chromosome segre- Available online 3 February 2016 gation during the first meiotic division. Crossovers are not distributed uniformly throughout the genome and are repressed at and near the centromeres. Rare crossovers that occur too near or in the centromere Keywords: interfere with proper segregation and can give rise to aneuploid progeny, which can be severely defec- Meiosis tive or inviable. We review here how crossing-over occurs and how it is prevented in and around the Homologous recombination Crossing-over centromeres. Molecular mechanisms of centromeric repression are only now being elucidated. How- Centromeres ever, rapid advances in understanding crossing-over, chromosome structure, and centromere functions Chromosome segregation promise to explain how potentially deleterious crossovers are avoided in certain chromosomal regions Aneuploidy while allowing beneficial crossovers in others. © 2016 Elsevier Ltd. All rights reserved. Contents 1.
    [Show full text]
  • The Drosophila Mei-S332 Gene Promotes Sister-Chromatid Cohesionin Meiosis Following Kinetochore Differentiation
    Copyright 0 1992 by the Genetics Society of America The Drosophila mei-S332 Gene Promotes Sister-Chromatid Cohesionin Meiosis Following Kinetochore Differentiation Anne W. Kerrebrock,* Wesley Y. Miyazaki,*9t Deborah Birnbyt”and Terry L. Orr-Weaver*9t92 *Whitehead Institute, Cambridge, Massachusetts 02142, and +Department ofBiology,Massachusetts Institute of Technology, Cambridge, Massachusetts 02142 Manuscript received September 3, 1991 Accepted for publication December24, 1991 ABSTRACT The Drosophila meiS332 gene acts to maintain sister-chromatid cohesion before anaphase I1 of meiosis in both males and females. By isolating and analyzing seven new alleles and a deficiency uncovering the mei-S332 gene we have demonstrated that the onset of the requirement for mei-S332 is not until late anaphaseI. All of our alleles result primarilyin equational (meiosis11) nondisjunction with low amounts of reductional (meiosis I) nondisjunction. Cytological analysis revealed that sister chromatids frequently separate in late anaphaseI in these mutants. Sincethe sister chromatids remain associated until late in the first division, chromosomes segregate normallyduring meiosis I, and the genetic consequencesof premature sister-chromatid dissociationare seen as nondisjunction in meiosis 11. The late onsetof mei-S332 action demonstratedby the mutations was not a consequence of residual gene function because two strong, and possibly null, alleles give predominantly equational nondis- junction both as homozygotes and in trans to a deficiency. mei-S332 is not required until after metaphase I, when the kinetochore differentiates from a single hemispherical kinetochore jointly organized by the sister chromatids into two distinct sister kinetochores.Therefore, we propose that the mei-S322 product acts to hold the doubled kinetochore together until anaphase 11.
    [Show full text]
  • S-Phase Checkpoint Genes Safeguard High-Fidelity Sister Chromatid Cohesion□D Cheryl D
    Molecular Biology of the Cell Vol. 15, 1724–1735, April 2004 S-Phase Checkpoint Genes Safeguard High-Fidelity Sister Chromatid Cohesion□D Cheryl D. Warren,* D. Mark Eckley,* Marina S. Lee,* Joseph S. Hanna,* Adam Hughes,* Brian Peyser,* Chunfa Jie,* Rafael Irizarry,† and Forrest A. Spencer*‡ *McKusick-Nathans Institute of Genetic Medicine, Ross 850, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and †Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205 Submitted September 2, 2003; Revised December 10, 2003; Accepted December 23, 2003 Monitoring Editor: Douglas Koshland Cohesion establishment and maintenance are carried out by proteins that modify the activity of Cohesin, an essential complex that holds sister chromatids together. Constituents of the replication fork, such as the DNA polymerase ␣-binding protein Ctf4, contribute to cohesion in ways that are poorly understood. To identify additional cohesion components, we analyzed a ctf4⌬ synthetic lethal screen performed on microarrays. We focused on a subset of ctf4⌬- interacting genes with genetic instability of their own. Our analyses revealed that 17 previously studied genes are also necessary for the maintenance of robust association of sisters in metaphase. Among these were subunits of the MRX complex, which forms a molecular structure similar to Cohesin. Further investigation indicated that the MRX complex did not contribute to metaphase cohesion independent of Cohesin, although an additional role may be contributed by XRS2. In general, results from the screen indicated a sister chromatid cohesion role for a specific subset of genes that function in DNA replication and repair. This subset is particularly enriched for genes that support the S-phase checkpoint.
    [Show full text]
  • Incomplete Y Chromosomes Promote Magnification in Male and Female Drosophila (Ribosomal Genes/Ribosomal Gene Amplification) DONALD J
    Proc. Nati. Acad. Sci. USA Vol. 84, pp. 2382-2386, April 1987 Genetics Incomplete Y chromosomes promote magnification in male and female Drosophila (ribosomal genes/ribosomal gene amplification) DONALD J. KOMMA AND SHARYN A. ENDOW* Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710 Communicated by D. Bernard Amos, December 12, 1986 ABSTRACT We have recently shown that magnification, on the Y that might encode a gene whose product initiates an increase in the number of ribosomal RNA genes (rDNA) in breaks in the rDNA or results in unequal pairing. Alterna- gametes produced by rDNA-deficient flies, can occur in female tively, the involvement of a limited region of the Y chromo- Drosophila if they have a Y chromosome. We now have tested some might imply a chromosomal pairing function analogous several X-Y translocation and recombinant chromosomes to to that of the collochores described by Cooper (8). determine which parts of the Y chromosome are necessary for The Ybb- chromosome, discovered by Schultz in 1933 (9), magnification to occur in females. Our data indicate that the has been described as being particularly effective in promot- required region is the distal part of the long arm of the Y ing magnification (1, 10, 11). In addition to promoting a high chromosome, yL. We have also used X-Y translocation chro- frequency of magnification in males carrying an Xbb chro- mosomes to study magnification of rDNA-deficient X chromo- mosome (1), it brings about the production of new bb alleles somes in males. Our data show that the region of the Y in males carrying an Xbb+ chromosome (2, 11, 12), and its chromosome from the distal end of the nucleolus organizer derivatives can bring about magnification of an Xbb chro- through the centromere is not required for magnfication in mosome in males of a bb+ phenotype (13), suggesting that it males.
    [Show full text]
  • H2A.Z Contributes to the Unique 3D Structure of the Centromere
    H2A.Z contributes to the unique 3D structure of the centromere Ian K. Greaves, Danny Rangasamy, Patricia Ridgway, and David J. Tremethick* The John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, The Australian Capital Territory 2601, Australia Edited by Steven Henikoff, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved November 1, 2006 (received for review September 10, 2006) Mammalian centromere function depends upon a specialized chro- In this study, we investigated: (i) whether H2A.Z is a core matin organization where distinct domains of CENP-A and di- constituent of pericentric heterochromatin; (ii) the interplay methyl K4 histone H3, forming centric chromatin, are uniquely between H2A.Z and CENP-A, including whether H2A.Z is a positioned on or near the surface of the chromosome. These component of centric chromatin; (iii) the 3D spatial organization distinct domains are embedded in pericentric heterochromatin of H2A.Z chromatin at metaphase and its relationship to the (characterized by H3 methylated at K9). The mechanisms that other marks of the centromere; and (iv) whether the histone underpin this complex spatial organization are unknown. Here, we modifications that define centric and pericentric chromatin in identify the essential histone variant H2A.Z as a new structural flies, humans (3), and fission yeast (7) are conserved in mice. component of the centromere. Along linear chromatin fibers H2A.Z is distributed nonuniformly throughout heterochromatin, and cen- Results tric chromatin where regions of nucleosomes containing H2A.Z and H2A.Z Is Present in Pericentric Heterochromatin at the Inner Centro- dimethylated K4 H3 are interspersed between subdomains of mere.
    [Show full text]
  • CHROMATID SEGREGATION of TETRAPLOIDS and HEXAPLOIDS HILDA GEIRINGER Wheaton College, Mass
    CHROMATID SEGREGATION OF TETRAPLOIDS AND HEXAPLOIDS HILDA GEIRINGER Wheaton College, Mass. Received February 26, 1949. INTRODUCTION N an earlier paper (GEIRINGER1948) the author has investigated the mathe- I matical genetics of autopolyploids if one locus is considered and chromo- some segregation is assumed. A paper on the linkage theory of autopolyploids (m loci), under the same assumption, is in press (GEIRINGER1949). However, while chromosome segregation might be assumed as an approximation theory, the study of polyploids should actually be based on the consideration of chromatid segregation. In the case of one locus this theory can be worked out and is presented in this paper as far as random mating is concerned. This study, for m = 1, as well as the approximation theory for general m, may serve as a necessary preparation for a general linkage theory of polyploids under chromatid segregation. A basic paper by J. B. S. HALDANE(1930) is mainly concerned with the chromosome segregation theory of polyploids; “random chromatid segrega- tion” of tetraploids is briefly discussed too and a limit formula (our formula (24)) follows. In a paper of a more recent date R. A. FISHER(1947) deals with the linkage theory of polyploids under chromatid segregation. The paper uses important earlier investigations by the same author (1941, 1944) as well as a paper by FISHERand MATHER(1943) and papers by MATHER(1935, 1936). As in previous papers it is our aim to consider a heredity problem like the one in question as a probability problem. From certain basic probability dis- tributions which must be known other genetical distributions are derived by means of probability calculus.
    [Show full text]
  • Teacher Background Meiosis
    Teacher Background Meiosis Note: The Teacher Background Section is meant to provide information for the teacher about the topic and is tied very closely to the PowerPoint slide show. For greater understanding, the teacher may want to play the slide show as he/she reads the background section. For the students, the slide show can be used in its entirety or can be edited as necessary for a given class. What are the two types of cell division? There are two types of normal cell division – mitosis and meiosis. Both types of cell division take place in eukaryotic organisms. Mitosis is cell division which begins in the zygote (fertilized oocyte) and continues in somatic cells throughout the life of the organism. Mitosis is important for growth and repair since this type of cell division produces genetically identical diploid copies of the original cell. (See chapter 2 for more details.) What is meiosis? Meiosis is cell division that occurs in the ovaries of the female and testes of the male and involves the maturation of primordial ooctyes (eggs) and formation of sperm cells, respectively. Primordial oocytes are present in the ovary at the birth of the female and sperm cells form from spermatogonia (sperm stem cells) in the testes. (See chapter 6 for more details.) Meiosis is a two-phase cell division process that reduces the chromosome number by half (haploid) so when fertilization occurs, the normal chromosome number of the species (diploid) will be maintained. Meiosis ensures genetic diversity by randomly assorting the homologous pairs of chromosomes as oocytes mature and sperm cells are formed.
    [Show full text]