Ch. 11:
Cell Cycle and Cell Division
Mette Voldby Larsen, CBS, DTU Systems Biology
Disposition
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Cell division in prokaryotes
Cell cycle in eukaryotes
Cell division in eukaryotes, part I: mitosis
BREAK
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Cell division in eukaryotes, part II: meiosis
Cell death
Cancer, oncogenes <> tumor supressors
Learning objectives
After this lecture you should be able to…
•  Account for the antiparallel double helical structure
of DNA and the chromosomal organization in proand eukaryotes.
•  Describe the mechanisms for bacterial cell
division and eukaryotic mitosis and meiosis and
suggest how failures in the two later processes
might lead to particular geno- or phenotypes.
Cell division consists of four steps:
  A
signal to divide
  DNA
replication
  DNA
segregation (separation)
  Cytokinesis
– dividing the cytoplasm
Prokaryotes
<>
Eukaryotes
Always single celled
Often multi cellular
Usually only one
chromosome per cell
Several chromosomes per cell
Usually a circular
chromosome
Linear chromosomes
One origin of replication
Several origins of replication
per chromosome
Divide as long as the
conditions are favorable
Cell division is carefully
restricted (in particular in
multicellular organisms)
Cell division in prokaryotes
– binary fission
Bacterial cell division: Salmonella enteritidis
Eukaryotic chromosomes
Here shown during metaphase (a phase of mitosis)
The chromosome consists of two sister chromatids held together at the centromere
Each chromatid consists of one DNA molecule
Organization of eukaryotic DNA
into chromosomes
DNA + histones
= chromatin
Cell cycle in eukaryotes
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M: Mitotic phase (mitosis +
cytokinesis) – the
chromosomes and the cell is
divided
G1: The chromosomes each
consist of one chromatid
  G0:
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No division
S: DNA synthesis (replication)
G2: The chromosomes each
consist of two chromatids
Regulating cell cycle
Cdk – cyclin dependent
kinase:
Phosphorylates other
proteins, e.g., the RB
protein
Cyclins:
-Cyclic presence
-Activates the Cdks
RB – retinoblastoma
protein:
Keeps the cell in G1,
when it is NOT
phosphorylated
Quiz for recapitulating the cell cycle
Cdk phosphorylates the RB protein
The cell passes the ”restriction point” and enters the S-phase of the cell cycle
The RB protein is inactivated
Cyclin binds and activates cdk
A growth factor stimulates the generation of cyclin
Cell division in eukaryotes
  Mitosis
(normal cell division):
Daughter cells are identical to the mother cell
Used for growth and asexual reproduction
  Meiosis
(for generating gametes):
Daughter cells only have half as many
chromosomes as the mother cell
Used for sexual reproduction
Mitosis
– the normal cell
division: Growth and
asexual
reproduction
Microtubules
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Part of the cytoskeleton
Long, hollow polymers of αTubulin and β-Tubulin
Dynamic: Can polymerize
and depolymerize
Centrosomes
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Also called the
"microtubule organizing
center"
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A centrosome consists
of two centrioles
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A centriole consists of 9
x 3 mikrotubules
Interphase
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The chromatin lies
entangled within the
nucleus. Individual
chromosomes cannot be
distinguished
The nucleus is surrounded
by the nuclear envelope
Inside the nucleus, a
nucleolus is present
During S-phase the
chromosomes and
centrosomes are replicated
1st step of mitosis
PROPHASE
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The chromatin condenses
and the chromosomes
become visible
The nucleolus disappears
The centrosomes move to
opposite poles of the cell
Microtubules extend from
the centrosomes thereby
forming the spindle
2nd step of mitosis
PROMETAPHASE
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The nuclear envelope
disintegrates
Microtubuli from the spindle
attach to the kinetochores
located at the centromers of
the chromosomes
3rd step of mitosis
METAPHASE
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Polymerization of the
microtobules from the poles
pushes the chromosomes
towards the center of the
cell
The centromers of the
chromosomes line up in the
equatorial plane of the cell
Each chromosome is
connected to both poles
through microtubules
4th step of mitosis
ANAPHASE
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The two cromatids of each
chromosome separate
The new daughter
chromosomes move
towards the poles of the cell
Two forces contribute to the
movement:

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Depolymerization of
microtubules at the poles
The motor protein dynein in
the kinetochores
5th step of mitosis
TELOPHASE
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The chromosome structure
disintegrates and the
chromatin re-entagles
The nuclear envelope
reforms
Cytokinesis: Dividing
the cytoplasm
Mitosis live
NB: In real life, this would take 4-5 hours
Cytokinesis
Animal cell: A contractile ring
pinches the cell in two
Plant cell: Membranous
vesicles fuse to form a cell
plate
BREAK
http://www.bjork.fr/Hollow-Clip
LO: Account for the antiparallel double helical structure of DNA
and the chromosomal organization in pro- and eukaryotes.
Typical exam question
(1 point): What is depicted in the figure below?
LO: Describe the mechanisms for bacterial cell
division and eukaryotic mitosis and meiosis and
suggest how failures in the two later processes
might lead to particular geno- or phenotypes.
Typical exam question (1 points): In which order do the
processes shown in picture A – F occur during mitosis?
A
C
E
B
D
F
Haploid and diploid cells
  Haploid:
  Diploid:
One set of chromosomes
Two sets of chromosomes
In diploid cells, the two chromosomes in a pair is
homologous meaning that they contain the same
genes (loci), but maybe in different versions
(different alleles).
The chromosomes of humans
A human cell contains 46 chromosomes:
•  22 autosomal chromosomes
•  Two sex-chromosomes
Cell division in eukaryotes
  Mitosis
(normal cell division):
Daughter cells are identical to the mother cell
Used for growth and asexual reproduction
  Meiosis
(for generating gametes):
Daughter cells only have half as many
chromosomes as the mother cell
Used for sexual reproduction
Meiosis
  One
diploid cell is divided twice to four haploid
cells
  Two divisions: meiose I og meiose II
  Much more rare than mitosis: Only occurs
during the generation of the gametes for
sexual reproduction
Meiosis I, prophase-prometaphase
NB: The homologous chromosomes pair up. This doesn’t happen
during mitosis.
Cross-over (recombination)
Chiasma
Meiosis I, metaphase-telophase
NB: The chromosomes that are separated during anaphase I still
contains two chromatids each – no degradation of the centromers
Meiosis II, prophase-anaphase
NB: Due to the cross-over events (the recombination), the cromatids that
are separated during anaphase may differ.
Meiosis II, telophase
Errors during meiosis
Non-disjunction: a pair of homologous
chromosomes are NOT separated during the
anaphase of meiosis I or the sister cromatids are
NOT separated during anaphase II
Following fertilization, the result is aneuploid cells
with one chromosome too many or too few.
Trisomi 21 (Down’s syndrom)
X0 (Turner-kvinde)
XXY (Klinerfelter mand)
Cell death

Necrosis: The cell is
starved, attacked or
poisoned

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Often many cells at once
Apoptosis (programmed
cell death): The cell
commits suicide following a
signal

Often a single cell
Apoptosis
Cancer, I
Oncogenes
-the speeder
-gain of function
Cancer, II
Tumor suppressors
-the break
-loss of function
Oncogen <> tumor suppressor
The speeder - oncogenes
Normale conditions
Enlarge speeder (oncogenes)
Lacking brake (tumor suppressor)
The brake- tumor suppressors
Is the RB protein an
oncogene or a tumor
suppressor?
RB – retinoblastoma
protein:
Keeps the cell in G1,
when it is NOT
phosphorylated