DNA and cell division

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DNA and cell division
Nara Institute of Science and Technology(NAIST)
Tatsuo Takeya
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Fact

• Each individual comprises a variety of cells
  containing identical genome
• Whereas offsprings contain different genetic
  information from those of parents and yet
  comprise the same repertoire of cells
• How can be these possible?

Question
Aim
Learn the basics of DNA and cell division so that
we can understand this phenomenon at the
molecular and cellular levels
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• Part I DNA
• Part II Cell division
• Part III Cell differentiation

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Part I

• From DNA to gene, and finally chromosome

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DNA deoxyribonucleic acids

• All genetic information is written in DNA
• It is conveyed by the sequence of its four
  nucleotide building blocks

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deoxy ATP
deoxy CTP
deoxy GTP
deoxy TTP
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Principles of DNA structure (1)
Polymer
Polarity
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Nucleotide sequence
Double-stranded
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Complementary base pairs AT
GC
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3
Source adapted from Molecular Biology of the
Cell
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Principles of DNA structure (2) double helix
Replication
Daughter cells
Source adapted from Molecular Biology of the
Cell
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DNA is a macromolecule
Genome the totality of genetic information
belonging to an organism
Human genome 3 x 109 nucleotides
DNA
(2 m)
Cell
(10 mm)
nucleus

• Fragmentation
• ? chromosome
• Packaging with the help of protein (histone)
• ? nucleosome structure

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Human genome and chromosomes
HumanGenome size3.2X109 nucleotides 22
autosomes and 2 sex chromosomes (X, Y)Diploid
(2n) (1-22) x 2 XY/XX 4635,000 genes?
Source adapted from Molecular Biology of the
Cell
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Higher structure of DNA and chromatin formation
chromatin
Nucleosome (DNA Histone)
Packaging into the nucleus
Source adapted from Molecular Biology of the
Cell
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Gene functional unit of genome
complementary to DNA
triplet of nucleotides (codon)? amino acid
Source adapted from Molecular Biology of the
Cell
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Chromosome and genes
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• Part II Cell division
• Transmission of genetic information to next
• generation and production of daughter cells

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Two types of cell division

• (Somatic) mitosis
• Genome information is preserved
• Two daughter cells are produced
• essential for development
• ?tissues, organs etc
• Meiosis
• Specific for gamete formation
• (oogenesis/spermatogenesis)
• Chromosome set 2n ? n
• Genetic information becomes altered
• essential for reproduction

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Mitosis
Cell cycle
segregation
duplication
cytokinesis
Source adapted from Molecular Biology of the
Cell
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Eukaryotic cell-cycle times

• Cell type
  Cell-cycle times
• Early frog embryo cells (egg cleavage)
  30 minutes
• Yeast cells
  1.5-3 hours
• Intestinal epithelial cells
  12 hours
• Mammalian fibroblasts in culture
  20 hours
• Human liver cells
  1 year

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Cell cycle regulation and check point
Unattached chromosome
Growthsignals
Unreplicated DNA
DNA damage
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Cytokinesis
eukaryotic cell
Source adapted from Molecular Biology of the
Cell
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Cell cycle regulation and check point
Unattached chromosome
Growthsignals
Cell mass including organellas
Unreplicated DNA
Cell mass
DNA damage
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Cytoskeletal machines operate mitosis
Source adapted from Molecular Biology of the
Cell
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Meiosis
A process producing germ cells (gamete)Unique
in that I) reduces genome ploidy
(diploid to haploid) II) induces genetic
variation
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Germ line
Meiosis
Source adapted from Molecular Biology of the
Cell
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I) Reduction of copy numbers
2n
4n
n
gametes
2n
Division II
Division I
Source adapted from Molecular Biology of the
Cell
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2n
Source adapted from Molecular Biology of the
Cell
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II) Genetic variation (1) mixing of chromosomes
Pairing and assortment of patternal and matternal
homologs
Independent assortment of each pair in division I
2n different haploid gametes (if n3)
Source adapted from Molecular Biology of the
Cell
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II) Genetic variation (2) exchange of genes
Crossingover/recombination between paired
homologs
Source adapted from Molecular Biology of the
Cell
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Genetic variations in germ cells
(if n3)
and so on
Source adapted from Molecular Biology of the
Cell
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Part III Cell differentiation
Mammals, in contrast to bacteria, consist of
various types of cells How can
be this achieved?
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Outline of hemapoiesis
Source adapted from Molecular Biology of the
Cell
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Prokaryotebinary fission
Simple duplication of identical cells
Source adapted from Molecular Biology of the
Cell
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Cell proliferation and differentiation
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• Proliferation increase of cell number
• Differentiation generation of diversity

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proliferation
Cell proliferation and differentiation in
development cell lineage

mitosis
progenitor
Stem cell

self-renewal

e.g., germ line hemopoiesis
differentiation
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How can be diversity generated?
Variations can be generated through controlled
gene expression
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Gene expression and control region
RNA polymerase
control region
On/Off
Source adapted from Molecular Biology of the
Cell
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Initiation and regulation of transcription
Essential components
On/Off
Source adapted from Molecular Biology of the
Cell
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Gene regulatory proteins
Each regulatory protein recognizes specific
nucleotide sequenceCombination of various
factors determines genes to be expressed
Source adapted from Molecular Biology of the
Cell
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Generation of diversity in cells
Extracellular stimuli
Intracellular signals
1 5regulatory proteins
Source adapted from Molecular Biology of the
Cell
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Methylation of DNA and gene silencing
Control region
Source adapted from Molecular Biology of the
Gene
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Epigenetic regulation (e.g, genome imprinting)
matternal and patternal chromosomes are not
equivalent in certain genes and only either
chromosome is active methylation is
central crucial for sexual reproduction and
development
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Oocytes and sperms
Continues to the following lectures---
Source adapted from Molecular Biology of the
Cell
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A question for essay/report

• How can be genetic variations generated
• through meiosis, not mitosis?