The Cell Cycle

Reading Alberts et al. 5th edition,

1053-1055, 1071-1080,
to change the H+ 1092-1094.
Lipid permeability O2 penetrates lipid bilayer faster than water (go back to that slide
ATP synthase can also go in the opposite direction gradient to go AGAINST the gradient by
CONSUMING ATP

Review Tutorial on Thursday 1

 Cell Division
• Cell division observed in a lung cell maintained
in cell culture

• From Alberts: 17.4-animal_cell_division.mov

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 The cell cycle
cells in a culture will not all be dividing, mostly spend time in interphase

• M phase:
– The nucleus and cytoplasm divide
• Mitosis nuclear division - chromosomes, etc.
• Cytokinesis cytoplasm/cells divide

• Interphase:
– The period between
cell divisions
• G1 phase
• S phase DNA replication~!!!!*****
• G2 phase

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Figure 17-4 Molecular Biology of the Cell (© Garland Science 2008)
 Cell cycles in multicellular organisms
1. Many mature cells do not divide:
– E.g. nerve cells, muscle cells, RBC
– As they became specialised they lost the ability
to divide.

2. Some cells only divide when given an

appropriate stimulus:
– E.g. liver cells
– When part of the liver is surgically removed the
remaining liver cells start to divide to replace
the lost tissue.

Stem cell
3. Some cells normally divide on an ongoing basis:
– E.g. Hematopoietic and epithelial stem cells
divide to blood cells epithelial

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 Cells that do not divide are in G0

Cell cycle exit

Cell does NOT divide (nerve cells

always here), but is NOT dead

DNA REPLICATION!!!
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 The cell-cycle control system
• Delays later events until
the earlier events are
complete
cells won't divide or move to next step until all
preparations are complete

• The major Checkpoints:

– Start checkpoint
– G2/M checkpoint
– Metaphase-to-anaphase
transition

Cyclin-dependent kynases (Cdks)

• kynases phosphorylate -
proteins to proteins name of checkpoint

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Figure 17-14 Molecular Biology of the Cell (© Garland Science 2008)
 M Phase

Figure 17-3 Molecular Biology of the Cell (© Garland Science 2008) * panel 17-1 7
 Prophase
• Replicated chromosomes
condense:
– Condensin protein complex

• Mitotic spindle assembly:

– Centrosome duplication (either end of the
cell
– Bipolar microtubules (tubulin made of two
parts - alpha, beta)

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 Chromosome condensation
centromere
• At the end of G2 the replicated
chromosomes are dispersed and
tangled

• At the beginning of mitosis

chromosomes condense
– condensin

'complex' - >1 protein, condense dna

• The sister chromatids are resolved but

remain associated

Figure 17-27 Molecular Biology of the Cell (© Garland Science 2008) 9

Figure 17-26 Molecular Biology of the Cell (© Garland Science 2008)
 Dynamic microtubules are required for mitosis
centrosome
• In an interphase cell:
– Microtubules are arranged in
a radial pattern
– Minus ends are stabilised at MTOC

• Prophase:
– Bipolar mitotic spindle
assembly starts
– Requires disassembly and reassembly of
microtubules
- because there are now TWO centrosomes,
and BOTH need microtubules surround centromere of chromosome

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Figure 16-30b Molecular Biology of the Cell (© Garland Science 2008)
 Centrosome structure
ONE CENTROSOME = TWO CENTRIOLES**** A tubule is the only complete
tubule
The centrosome MTOC:
Microtubule organising centre

A pair of centrioles:
– Organised at right angles to each
other
– Composed of:
• Nine
Nine fibrilsfibrils
of threeofmicrotubules
three microtubules
each A nucleated
each microtubule

Surrounded by:
– Pericentriolar material protein cloud here
γ-tubulin ring
– gamma-tubulin complexes
ring complexes, (y-TuRCs)
is the
pericentriolar
(γ-TuRCs) material

sticks out from "cloud"

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 The γ-tubulin ring complex
regular a-B tubulin
γ-TuRCs:
- A complex of proteins forms a ring
structure (green)

plus - γ-tubulin (orange) binds the ring

structure and acts as an attachment
site for α/β-tubulin dimers.

gamma-tubulin
- Forms a stabilising cap at the microtubule
minus minus end
γ-TuRC
lots of proteins (together make the y-TuRC!!)

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A similar structure is shown in Figure 16-29 Molecular Biology of the Cell (© Garland Science 2008)
Centrosome duplication and mitotic spindle assembly
CENTRIOLES ARE ALWAYS AT RIGHT ANGLES TO EACH OTHER

• Centrosome duplication:
– STARTS IN 'S' PHASE

• Bipolar mitotic spindle

assembly:
– STARTS IN 'M' PHASE
(prophase)

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 Centrosome duplication is
semi-conservative
• Each centriole serves as a template for a new centriole.

• CENTROSOMES ARE DUPLICATED ONLY ONCE PER CELL CYCLE

- like DNA, multiplies once, and uses old as a template for new centriole

Complete mitotic
spindle assembly
requires nuclear
envelope breakdown

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Figure 17-31 Molecular Biology of the Cell (© Garland Science 2008)
 Nuclear envelope breakdown
* OCCURS AT THE BOUNDARY BETWEEN PROPHASE AND PROMETAPHASE

Nuclear lamina: Meshwork of interconnected nuclear

lamin proteins

Lamin: A special class of intermediate filaments that

form a two-dimensional lattice on the inner nuclear
membrane

-Phosphorylation of lamins is thought to trigger

(Late)
nuclear envelope breakdown cyclin-dependent kynases will phosphorylate
the laminins, which won't associate with each other and DNA, so nuclear
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Figure 12-20 Molecular Biology of the Cell (© Garland Science 2008) envelope breaks down
 Prometaphase
• Mitotic spindle assembly is
completed

• Chromosomes attach to
spindle microtubules

• Chromosome movement
begins

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 Mitotic spindle assembly
need dynamics, can break down and reform; also need transport - the dyneines and kynases walkie-guys that transport things

interact with cell cortex to chromosomal microtubules keeps centrosomes apart

anchor the mitotic spindle 20-30 microtubules 17
Figure 17-28 Molecular Biology of the Cell (© Garland Science 2008)
 Microtubule motor protein activity
walkie-guys move chromsomes

moves to +ve end

moves to -ve end

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Figure 17-30 Molecular Biology of the Cell (© Garland Science 2008)
 Mitotic Spindle
• A 3D reconstruction of the mitotic spindle

• From Alberts: 17.7-mitotic_spindle.mov

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 Metaphase
• All chromosomes are
aligned:
– sister chromatids along centre of cell

• Microtubules from
opposite poles:
– are attached to
kinetochores of sister
chromatids

• Kinetochores are located:

– in middle

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 Mitotic spindle assembly

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Figure 17-28 Molecular Biology of the Cell (© Garland Science 2008)
 Chromosome attachment to microtubules

collar structure - if microtubules

assemble/polymerise, it'll move right;
if it depolymerises, it'll go left

appropriate amount of tension from both sides

end of metaphase, the cell has two centrosomes!

Figure 17-37 Molecular Biology of the Cell (© Garland Science 2008)
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Figure 17-39 Molecular Biology of the Cell (© Garland Science 2008)
 The metaphase-anaphase transition
• http://www.youtube.com/watch?v=P7m3WfzgZdI

• Cell division in a kidney epithelial cell

• Notice that anaphase does not start until all the
chromosomes are aligned on the metaphase plate
 an important checkpoint

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 Anaphase
• Sister chromatids separate
to form the two daughter
chromosomes

• They are pulled towards

opposite poles

• Kinetochore microtubules:
– end
shortening, brings chromosomes toward either
of cells

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 Kinetochore microtubule shortening
anaphase A

Anaphase A

Figure 17-46 Molecular Biology of the Cell (© Garland Science 2008) anaphase B
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Figure 17-40 Molecular Biology of the Cell (© Garland Science 2008) spindle poles move apart
 Telophase
• Nuclear envelope
reassembly:
– Marks the end of Mitosis

the plus ends get longer and push each other

apart

microtubules depolymerise in anaphase A

spindle poles move apart in anaphase B

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 Nuclear envelope reassembly

slowly reassembling nucleus

structure form around the chromosomes

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Figure 12-20 Molecular Biology of the Cell (© Garland Science 2008)
 Cytokinesis
• Cytoplasm divided in
two:
– by a contractile ring of:
 actin and myosin

• The interphase microtubules

reform in each daughter cell
not in spindle formation anymore

• Marks the end of M phase

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 The cleavage furrow
• Cytokinesis requires:
– dynamic actin filaments

• At the beginning of forms under the cell membrane, drags

membrane with it

mitosis actin and myosin

arrays disassemble

• They assemble at the

contractile ring at the end
of mitosis.

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Figure 17-49 Molecular Biology of the Cell (© Garland Science 2008)
 Cell Division plant cells
• In animal cells the cytoplasm is divided by
cytokinesis.
• In plant cells…
in plants, a membrane forms between the cells, then becomes the cell wall

• From Alberts: 17.3-plant_cell_division.mov

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 Many cell divisions are required to
produce a multicellular organism

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Figure 17-9 Molecular Biology of the Cell (© Garland Science 2008)
 Meiosis

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Figure 17-47 Molecular Biology of the Cell (© Garland Science 2008)
 Cell differentiation is required to
produce a multicellular organism

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Figure 17-9 Molecular Biology of the Cell (© Garland Science 2008)
- can change into ANY kind of cell
- adults have haematopoetic stem cells, can only be one thing

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Adult Stem Cells

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 Life inside the cell
• Shown at the beginning of the course.
• We have talked about several of the processes
shown in this animation.

http://multimedia.mcb.harvard.edu/media.html

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