2010 Lecture 16

Cell Division

Historic Historic 1882 mitosis drawings

Introduction

How does one cell become two?

Cell Cycle | Movie of mitosis in the embryo

Movies

• Movie - ASCB Mitosis in a Vertebrate Cell
• JCB - Movie Collection Mitosis | Cytokinesis

• 2009 Lecture - Cell Division 2008 ANAT3231 Lecture PDF lecture14-15 1 slide/page (view) | 4 slides/page (print) | 6 slides/page (print) | text (print)

Cell Division

• Cell Division Milestones
• Recent Nobel Prizes- 2001 Cell Cycle, 2002 Cell Death

Features 2 mechanical processes

• Mitosis segregation of chromosomes and formation of 2 nuclei
• Cytokinesis splitting of the cell as a whole into 2 daughter cells

Textbooks

• Essential Cell Biology (Alberts) Chapter 17
• Molecular Biology of the Cell (Alberts) – Chapter 17,18
• The Cell – Chapter 14,15
• Molecular Cell Biology – Chapter 13

Binary Fission

• Prokaryotes – And Eukaryote mitochondria
• Asexual reproduction - replicates original cell to produce two identical cells
• Grow in numbers exponentially
  • adequate nutrients and a fast life cycle
  • single organism can multiply into billions
• High mutation rate of bacteria

(fission = splitting of something into its parts)

Cell Lifespan

• Body cell types – About 210 types
• Lifespan – Born, Differentiate, Function, Divide or Die

Cell Types

• Neutrophil – 6-7 hours circulating – 4 days in tissue
• Red blood cell – 120 days
• Brain neuron, heart – 50 - 100 years

Cell Changes

• Nucleus
  • Chromosome condensation
  • Nuclear envelope breakdown

• Cytoplasm
  • Cytoskeleton reorganization
  • Spindle formation (MT) Contractile ring (MF)
  • Organelle redistribution

• Mitosis Energy
  • Cell division uses up a lot of energy, so cells ensure they have enough resources to complete the job before committing to it.

Mitosis Phases

• Based on light microscopy of living cells light and electron microscopy of fixed and stained cells
• 5 Phases - prophase, prometaphase, metaphase, anaphase, and telophase
  • Cytokinesis 6th stage overlaps the end of mitosis

MBC The stages of mitosis and cytokinesis in an animal cell

Interphase

• not a mitotic phase (discussed in cell cycle)
• Chromosomes dispersed in nucleus
• Gene expression
• Cytoskeleton and cell organelles - Distributed and functioning
• Mitochondria undergo independent proliferation/division

Chromosome Changes

Prophase

Mammalian cell - prophase

• Chromosome DNA has been earlier duplicated (S Phase)
• Chromosomes begin condensing
• Chromosome pairs (chromatids) held together at centromere

• Microtubules disassemble
• Mitotic spindle begins to form

Spindle Apparatus

• 3 sets of microtubules - (+) ends point away from centrosome at each pole.

1. astral microtubules - anchor the pole end in position
2. kinetochore microtubules - connected to chromosomes
3. polar microtubules - form the structure of the spindle apparatus

Spindle Apparatus EM | Spindle Apparatus | MBC Movie- Microtubule dynamics during mitosis

At end of prophase nuclear envelope breaks down

Prometaphase

• Microtubules now enter nuclear region
• Nuclear envelope forms vesicles around mitotic spindle
• Kinetochores form on centromere attach to some MTs of spindle

Dynamic instability and the capture of chromosomes

Centromeric attachment of microtubules

At end of prometaphase chromosomes move to metaphase plate

Metaphase

Mitosis - Metaphase

• Kinetochore MTs align chromosomes in one midpoint plane

Proposed alternative mechanisms for chromosome congression

Metaphase ends when sister kinetochores separate

Anaphase

Chromosome motility anaphase

• Separation of sister Kinetochores
• shortening of Kinetochore microtubules pulls chromosome to spindle pole

Experiment - during anaphase A chromosomes move poleward along stationary kinetochore microtubules, which coordinately disassemble from their kinetochore ends

Anaphase ends as nuclear envelope (membrane) begins to reform

Telophase

Mitosis - Telophase

• Chromosomes arrive at spindle poles
• Kinetochore MTs lost
• Condensed chromosomes begin expanding
  • Continues through cytokinesis

Links: Figure 19-41 Microtubule dynamics during mitosis | Figure 19-34. The stages of mitosis and cytokinesis in an animal cell | Cytokinetic abscission: cellular dynamics at the midbody

Cytokinesis

• Division of cytoplasmic contents
• Contractile ring forms at midpoint under membrane
• Microfilament ring - contracts forming cleavage furrow
  • myosin II is the motor
• Eventually fully divides cytoplasm

Links: Cytokinesis | Cytokinesis in Plants

Cell Organelles

Mitochondria

• Divide independently of cell mitosis
• distributed into daughter cells

Peroxisomes

• localise at spindle poles

Golgi

Post-mitotic Golgi stack formation

• 2 processes - disassembly and reassembly
• Golgi stack undergoes a continuous fragmentation process
• fragments are distributed into daughter cells
• are reassembled into new Golgi stacks

Disassembly

• Unstacking - mediated by two mitotic kinases (cdc2 and plk)
• Vesiculation - mediated by COPI budding machinery ARF1 and the coatomer complex

Reassembly

• Fusion - formation of single cisternae by membrane fusion
• Restacking - requires dephosphorylation of Golgi stacking proteins by protein phosphatase PP2A

Links: Tang D, Mar K, Warren G, Wang Y. Molecular mechanism of mitotic Golgi disassembly and reassembly revealed by a defined reconstitution assay. J Biol Chem. 2008 Mar 7;283(10):6085-94. Epub 2007 Dec 21. PMID: 18156178

Mitosis and Meiosis

Progeny

Mitosis 2 Daughter cells identical to parent (diploid)

Meiosis Germ cell division (haploid)

• Reductive division
• Generates haploid gametes (egg, sperm)
• Each genetically distinct from parent

• Genetic recombination (prophase 1)
  • Exchanges portions of chromosomes maternal/paternal homologous pairs
• Independent assortment of paternal chromosomes (meiosis 1)

Cell Birth - Mitosis and Meiosis 1st cell division- Meiosis

Homologous chromosomes pairing unique to meiosis

• Each chromosome duplicated and exists as attached sister chromatids before pairing occurs
• Genetic Recombination shown by chromosomes part red and part black
  • chromosome pairing in meiosis involves crossing-over between homologous chromosomes

(For clarity only 1 pair of homologous chromosomes shown)

Comparison of Meiosis/Mitosis

• After DNA replication 2 nuclear (and cell) divisions required to produce haploid gametes
• Each diploid cell in meiosis produces 4 haploid cells (sperm) 1 haploid cell (egg)
• Each diploid cell mitosis produces 2 diploid cells

Abnormalities

Meiotic Nondisjunction

• Occurs when homologues fail to separate during meiotic division I or II
• Down Syndrome
• Caused by an extra copy of chromosome 21

Nondisjunction

Chromosomal Translocations

• Philadelphia chromosome
• Chronic myelogenous leukemia
  • Piece of Chr9 exchanged with Chr22 Generates truncated abl

Overstimulates cell production

Meiosis Sex Differences

Female (oogenesis)

• Meiosis initiated once in a finite population of cells
• 1 gamete produced / meiosis
• Completion of meiosis delayed for months or years
• Meiosis arrested at 1st meiotic prophase and reinitiated in a smaller population of cells
• Differentiation of gamete occurs while diploid in first meiotic prophase
• All chromosomes exhibit equivalent transcription and recombination during meiotic prophase

Male (spermatogenesis)

• Meiosis initiated continuously in a mitotically dividing stem cell population
• 4 gametes produced / meiosis
• Meiosis completed in days or weeks
• Meiosis and differentiation proceed continuously without cell cycle arrest
• Differentiation of gamete occurs while haploid after meiosis ends

Sex chromosomes excluded from recombination and transcription during first meiotic prophase

References

Textbooks

Essential Cell Biology

• Essential Cell Biology Chapter 17

Molecular Biology of the Cell

Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002

• Molecular Biology of the Cell 4th ed. - IV. Internal Organization of the Cell Chapter 17. The Cell Cycle and Programmed Cell Death
• The Cell Cycle and Programmed Cell Death
• An Overview of the Cell Cycle
• Figure 17-1. The cell cycle

Molecular Cell Biology

Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999

• Figure 19-41 Microtubule dynamics during mitosis
• Figure 19-34. The stages of mitosis and cytokinesis in an animal cell

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

• The Cell - A Molecular Approach - IV. Cell Regulation Chapter 14. The Cell Cycle
• The Eukaryotic Cell Cycle
• Figure 14.1. Phases of the cell cycle

Search Online Textbooks

• "cell division" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf

• "mitosis" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf

• "meiosis" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf

PubMed

• PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed

• PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC

• Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM

• Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez

Search Pubmed

• "cell division" Entrez all databases
• "mitosis" Entrez all databases
• "meiosis" Entrez all databases
• "cyokinesis" Entrez all databases

Reviews

• The great divide: coordinating cell cycle events during bacterial growth and division. Haeusser DP, Levin PA. Curr Opin Microbiol. 2008 Apr;11(2):94-9. Epub 2008 Apr 7. Review. PMID: 18396093 | PMC

• Cell cycle studies based upon quantitative image analysis. Stacey DW, Hitomi M. Cytometry A. 2008 Apr;73(4):270-8. Review. PMID: 18163464

• Analysis of cell cycle phases and progression in cultured mammalian cells. Schorl C, Sedivy JM. Methods. 2007 Feb;41(2):143-50. Review. PMID: 17189856

• Cell cycle regulation of DNA replication. Sclafani RA, Holzen TM. Annu Rev Genet. 2007;41:237-80. Review. PMID: 17630848

External Links

• ASCB iBioSeminars - Separating Duplicated Chromosomes by Dick McIntosh - Part 1: Preparing for Cell Division | Part 2: Understanding Mitosis through Experimentation | Part 3: Moving Chromosome to the Spindle Poles: the mechanisms of anaphase A

• McGraw-Hill Animation comparing Mitosis and Meiosis
• Salmon Lab Mitosis Movies

2010 Course Content

Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cell Mitochondria | Cell Junctions | Cytoskeleton Introduction | Cytoskeleton 1 Intermediate Filaments | Cytoskeleton 2 Microtubules | Cytoskeleton 3 Microfilaments | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | Revision

Laboratories: Introduction to Lab | Microscopy Methods | Preparation/Fixation | Immunochemistry | Cell Knockout Methods | Cytoskeleton Exercise | Confocal Microscopy | Microarray Visit | Tissue Culture 1 | Tissue Culture 2 | Stem Cells Lab | Stem Cells Analysis

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G