The Cell Cycle

Reading Alberts et al. 5th edition,

1054-1055, 1071-1078, 710-712, 992996, 1092-1094.
Review Tutorial on Thursday
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Cell Division
Cell division observed in a lung cell maintained
in cell culture

From Alberts: 17.4-animal_cell_division.mov

The cell cycle

M phase:

very few cells are dividing at any given time

The nucleus and cytoplasm divide

Mitosis (nuclear division)
Cytokinesis (cytoplasmic division)

Interphase:
The period between
cell divisions
G1 phase (gap 1)
S phase (synthesis)
G2 phase (gap 2)

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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:

2.

Some cells only divide when given an

appropriate stimulus:

3.

E.g. nerve cells, muscle cells, RBC

As they became specialised they lost the ability
to divide.

E.g. liver cells

When part of the liver is surgically removed the
remaining liver cells start to divide to replace
the lost tissue.

Some cells normally divide on an ongoing basis:

Stem cell

E.g. Hematopoietic and epithelial stem cells

continuing dividing to maintain a stable population

Cells that do not divide are in G0

and cytokinesis

cell cycle exit

The cell-cycle control system

Delays later events until
the earlier events are
complete
The major Checkpoints:
Start checkpoint
G2/M checkpoint
Metaphase-to-anaphase
transition
cyclins are made if checkpoints met

cyclin-dependent kinases
(Cdks)
phosphorylate other proteins
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Figure 17-14 Molecular Biology of the Cell ( Garland Science 2008)

M Phase
cytokinesis starts before mitosis is finished

M-Cdk activation drives entry into mitosis:

M-Cdk phosphorylates proteins involved in mitotic spindle assembly,
chromosome condensation, and nuclear envelope breakdown

Figure 17-3 Molecular Biology of the Cell ( Garland Science 2008)

* panel 17-1

Prophase
Replicated chromosomes
condense:

condensin protein complex

Mitotic spindle assembly:

centrosome duplication
bipolar microtubules

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

centromere

At the beginning of mitosis

chromosomes condense
condensin
(5-protein complex)

The sister chromatids are resolved but

remain associated

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

Figure 17-26 Molecular Biology of the Cell ( Garland Science 2008)

Dynamic microtubules are required for mitosis

In an interphase cell:

centrosome

Microtubules are arranged in

a radial pattern
minus ends stabilised at MTOC

Prophase:
Bipolar mitotic spindle is
assembled
requires disassembly and reassembly
of microtubules

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Figure 16-30b Molecular Biology of the Cell ( Garland Science 2008)

Centrosome structure
The centrosome MTOC:
A pair of centrioles:
Organised at right angles to each
other

Composed of:

nine fibrils of 3 microtubules

each

A nucleated
microtubule

Surrounded by:
Pericentriolar material (in blue)
gamma-tubulin ring complexes
(gamma-TuRCs)

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The -tubulin ring complex

-TuRCs:
- A complex of proteins forms a ring
structure (green)
- -tubulin (orange) binds the ring
structure and acts as an attachment
site for /-tubulin dimers.

plus

minus

-TuRC

forms stabilising cap at minus end of

microtubule

A similar structure is shown in Figure 16-29 Molecular Biology of the Cell ( Garland Science 2008)

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Centrosome duplication and mitotic spindle assembly

Centrosome duplication:
starts in S phase

Bipolar mitotic spindle

assembly:
starts in M phase
(prophase)

1 centrosome
2 centrioles

1 centrosome
2 big centrioles
2 small centrioles

2 centrosomes
4 centrioles

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

centrosomes duplicated only once per cell cycle

Complete mitotic
spindle assembly
requires nuclear
envelope breakdown

green is PCM

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Figure 17-31 Molecular Biology of the Cell ( Garland Science 2008)

Nuclear envelope breakdown

*

occurs at 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 nuclear envelope breakdown

(Late)
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Figure 12-20 Molecular Biology of the Cell ( Garland Science 2008)

Prometaphase
Mitotic spindle assembly is
completed
start to get pushed together

Chromosomes attach to
spindle microtubules
Chromosome movement
begins

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Mitotic spindle assembly

polymerization required

help position
spindle
Figure 17-28

interdigitate
(chromosomal microtubules)
help position
17
go from spindle pole to kinetochore
spindle
Molecular Biology of the Cell ( Garland Science 2008)

Microtubule motor protein activity

lots of different proteins help position things

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Figure 17-30 Molecular Biology of the Cell ( Garland Science 2008)

Metaphase
All chromsomes are
aligned:

on the metaphase plate

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

Kinetochores are located:

at the centromere

kinetochores are large protein

structures
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Chromosome attachment to microtubules

single spindle
binds to 1 kinetochore

then, more bind

in different
ways

collar structure
surrounding microtubial
plus end

kinetochores bound
tightly, and pulled
Figure 17-37 Molecular Biology of the Cell ( Garland Science 2008)
Figure 17-39 Molecular Biology of the Cell ( Garland Science 2008)

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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:
shorten

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Kinetochore microtubule shortening

anaphase A
pole-ward microtubial flux
+ and - end depolymerization occurs

anaphase B

2 spindle poles are moving apart

Figure 17-46 Molecular Biology of the Cell ( Garland Science 2008)motor
Figure 17-40 Molecular Biology of the Cell ( Garland Science 2008)

proteins are pushing the 2 apart

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Telophase
Nuclear envelope
reassembly:
Marks the end of Mitosis
but not of M-phase

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Nuclear envelope reassembly

eventually membranes all fuse together

reassembles lamins
start reforming nuclear
membrane around each
chromosome

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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
Marks the end of M phase

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The cleavage furrow

actin and myosin help cells move, used for muscle contraction, used for cytokinesis

Cytokinesis requires:

dynamic actin filaments

At the beginning of
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)

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)

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Adult Stem Cells

32

End

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