The Cell Cycle: cell division and mitosis (and meiosis)

Chap. 11
Cell division reproduces an entire organism:
prokaryotes and single-celled eukaryotes divide
into 2 cells, each an individual organism

Cell division allows multi-cellular organisms to develop

from single cells: embryo development in sea urchin

Cell division functions in renewal and repair: dividing

bone marrow cells give rise to new blood cells

Omnis cellula e cellula (Latin) = Every cell from a cell

Key concepts cell cycle

New cells arise from pre-existing cells = cell division, part of cell cycle
Cell cycle = cell growth + division of the nucleus and genetic material
(mitosis), cytoplasm and organelles (cytokinesis)
Prior to cell division DNA is replicated but the nucleus/genetic
material can then divide in two very different ways
- mitosis: genetic material is copied and divided equally so daughter
cells are genetically identical to the parent cell
- [meiosis: results in daughter cells (eggs and sperm) that are
genetically different with half the amount of genetic material as the
parent cells]
Cell cycle is tightly regulated (molecular checkpoints)
Why you should care: a) breakdown of cell cycle control leads to
cancer; b) number of cell divisions is related to ageing and lifespan

The cell cycle has four phases (Fig. 11.3)

M- (mitotic) phase
= dividing phase
mitosis + cytokinesis
I- (interphase) phase
= non-dividing phase
G1 = first gap phase
S = synthesis phase
G2 = second gap phase

Cell growth occurs in all 3 I-phases; including replication of all cell

organelles/membranes

DNA replication occurs in S-phase, i.e. chromosomes are copied

Chromosomes, histones and chromatin a refresher

A chromosome consists of a
single, long DNA molecule
wrapped around histone proteins
forming nucleosomes
DNA + proteins = chromatin
Proteins help fold DNA molecules
(2 m of DNA = 250,000 x cell diameter)

Chromatin has several levels of

organisation (Fig. 18.2)
Fig. 18.2

Each chromosome carries several

hundred to a few thousand genes

Genome = the cells total amount

of DNA (multiple chromosomes)

Topic of the week!

Chromosome morphology changes during cell cycle

replicated (copied) before mitosis = sister chromatids
condensed at start of mitosis (can be moved around cell easily)
Non-dividing cell

Fig. 11.2

DNA replication

Sister chromatids are held together at the centromere and by cohesin

proteins (see Fig. 11.4)
During mitosis one of the sister chromatids (chromosome copies) is
distributed to each of the two daughter cells that form during cell division

How does the cell move sister chromatids to the poles

(opposite ends) during mitosis?: the mitotic spindle
Spindle is a microtubule structure with
associated motor proteins that begins to
assemble in prophase

(Polar)

Fully formed mitotic

spindle during metaphase

Some microtubules (kinetochore

microtubules) capture sister chromatids
by binding to kinetochore
Other nonkinetochore microtubules and
shorter asters also form part of spindle

Mitosis is broken down into five phases PPMAT

(and interphase makes six!) Fig. 11.5
Prophase

Prometaphase

Metaphase

Interphase

G2 interphase: nuclear envelope intact; chromosomes duplicated (by G2) but not
condensed (long and thin!); centrosome has duplicated

Prophase: chromosomes condense, centrosomes move away from each other,

mitotic spindle starts to form

Prometaphase: nuclear envelope disintegrates, kinetochore microtubules contact

chromosomes at kinetochore

Metaphase: chromosomes complete migration to middle of cell

Mitosis is broken down into five phases PPMAT

(and interphase makes six!) Fig. 11.5
Anaphase

Telophase

Anaphase: sister chromatids separate; chromosomes are pulled to

opposite poles of the cell as kinetochore microtubules shorten

Telophase: nuclear envelope reforms; spindle disintegrates

Cytokinesis: cell division occurs

Light micrographs of REAL lung cells dividing in a newt

How do chromosomes move during mitosis? (Fig. 11.8)

Spindle apparatus is made of microtubules

Microtubules are polymers composed of and -tubulin sub-units (monomers)

Kinetochore microtubules
shorten during anaphase due to
loss of tubulin sub-units
As they shorten, motor proteins
walk the chromosomes down
the remaining length of
microtubule to the poles of the
dividing cells
Fig. 11.9

Cytokinesis results in two daughter cells

Cytokinesis = separation of
cytoplasm + organelles into two
daughter cells
Occurs by a process called
cleavage
Cleavage furrow forms on cell
surface
Caused by a contractile ring of
actin microfilaments which
interact with myosin molecules
to contract ring
Works like drawstring
pinching parent cell into two
daughter cells

Fig. 11.6

Control of the cell cycle: when does a cell divide and

when does it stop dividing? (Fig. 11.14)

Checkpoints involve molecular

signals that report whether
critical cellular processes that
should have occurred by that
point have been completed
correctly
Cell size sufficient
DNA undamaged
DNA replicated OK
Social signals present
Molecular signals (MPF) present

Cell cycle

3 key checkpoints: G1, G2 and Metaphase

Frequency of cell divisions and importance of

molecular checkpoints varies with the type of cell
Human skin and gut cells divide
frequently throughout life

Some cells do not divide but retain

the ability to divide, e.g. if damaged
Liver

Fully formed muscle and nerve cells

do not divide at all in mature human
(= G0 phase)
These cell cycle differences result from regulation at the molecular level
(mainly variation in the length of G1 phase)

MPF (mitosis-promoting factor) is a general molecular

signal at the G2 checkpoint that says start mitosis

MPF consists of a cyclindependent protein kinase (Cdk)

- constant concentration
(green line)
+ a cyclin (regulatory protein)
- concentration fluctuates
through cell cycle
(blue line)

As cyclin increases during interphase more and more associates

(dimerizes) with Cdk to form MPF
This activates the protein kinase component of MPF
The kinase sub-unit catalyzes the phosphorylation of other proteins to
start mitosis ON switch
During anaphase enzymes degrade cyclin sub-unit OFF switch

Other signals contribute to regulation of cell cycle

Cells fail to divide (in culture) if essential nutrients and growth factors
are lacking
Growth factors are called social signals = proteins that stimulate other
cells to divide

If DNA is damaged the protein p53 activates genes that stop the cell
cycle and cause programmed cell death or apoptosis
Crowded cells stop dividing = density-dependent inhibition

When cell-cycle control fails = uncontrolled cell division = cancer,

due to:
a) defects that make proteins required for cell growth active when
they shouldnt be
b) defects that prevent tumour suppressor genes from shutting down
cell division

Why should you care? Loss of cell cycle control in

cancer cells cause tumor formation

Mutation or defects in one or more genes results in faulty cell cycle control
e.g. abnormally high expression of HER2 and ER, defective Ras

Cell transforms into cancer cell cells divide rapidly (proliferate) in

uncontrolled manner to form tumor
Cancer cells are also invasive: able to spread through the body in blood or
lymph system

Meiosis results in reduction in genetic material:

each daughter cell contains only half as many chromosomes as
parent cell (diploid to haploid)

Fig. 12.8

See Summary Table 12.3 pg. 240 for

Key differences between mitosis
and meiosis

Cool story: What do ribs do? What is their function?

Self-mutilation as a defence tactic in the Spanish ribbed newt Pleurodeles
waltl

When attacked by a predator the newt swings its ribs forward and
bursts them through its own skin
The rib barbs get coated in a poisonous fluid from glands on the
skin (orange)
After the attack the newt simply pops its ribs back inside its body and
regenerates new skin (and it doesnt infect itself!)