1. The cytoskeletal system, cell
cycle and DNA replication
Hilary Mok
Yolande Leong
BMS/1M02
Cheesecake!

2. The Cytoskeletal System
• An intricate network of protein filaments that
extend throughout the cytoplasm
• Highly dynamic->continuously reorganised as
a cell changes shape, divides and responds to
its environment

3. Functions of the cytoskeleton
• Establishes cell shape
• Provides mechanical
strength
• Locomotion
• Chromosome separation
in mitosis and meiosis

4. Components of cytoskeletal system
1. Intermediate Filaments
2. Microtubules
3. Actin Filaments
• Each type of filament has distinct mechanical
properties and is formed from a different protein
subunit.
• Thousands of these subunits come together to
form a fine thread of protein

5. Intermediate filaments (IF)
• 8-10nm
• Strong and Rope-like
• Form a network throughout the cytoplasm of
most animal cells
• Toughest and most durable of the three
• Can survive concentrated salt solutions and
non-ionic detergents

6. Functions & Properties of IF
• Have great tensile strength for structural
support
• Strengthens cells against mechanical stress
when stretched
• Maintenance of animal cell shape
• Stabilised and reinforced by accessory
proteins (e.g. plectin)

7. Categories of IF
Intermediate Filaments
Cytoplasmic Nuclear
Vimentin and
Keratins Vimentin-related Neurofilaments Nuclear Lamins
filaments
In (mostly) In connective In nerve cells In all animal cells
epithelial cells tissue, muscle
cells and glial
cells

8. Cytoplasmic IF
• Keratin
– Span interiors of epithelial cell from one
side to the other
– Forms a cable of high tensile strength which
distributes stress exerted on the skin cell
• Vimentin and Vimentin-related filaments
– Maintain cell shape for glial cell
– Provide structure support for contractile
machinery
• Neurofilaments
– Supports axon growth

9. Nuclear IF
• Nuclear lamina
– Just beneath nuclear membrane
– Underlies and strengthens the nuclear envelope in
all eukaryotic cells
– Other types extends across the cytoplasm, giving
cells mechanical strength

10. Hutchinson-Gilford Progeria Syndrome
(HGPS)
• Caused by mutation of gene
that encodes for Lamin A
• Not hereditary
• Rare and fatal condition, no
cure
• Cell nucleus has aberrant
morphology as compared to
a normal cell nucleus

11. • Affects children of all ethnicity
• Cause individuals to appear to
age prematurely
• Signs: growth failure, loss of
body fat and hair, wrinkled skin,
stiffness in joints,
atherosclerosis, stroke
• Patients die young, ranging
from 8-21, averaging at 13

12. Ashley Hegi, 16

13. Microtubules
• Long, hollow cylinder , made from the protein
tubulin
• 25nm in diameter
• More rigid than actin filaments
• Normally have one end attached to a
centrosome.
• 2 types : Axonemal microtubules and
Cytoplasmic microtubules

14. Axonemal microtubules
• Highly organised, stable microtubules in
specific subcellular structure associated with
cellular movements (E.g. cilia, flagella)

15. Cytoplasmic microtubules
• Loosely organised, dynamic
network of microtubules
• Variety of functions: formed
mitotic and meiotic spindles,
required from movements of
chromosomes during mitosis
and meiosis
• Provides an organised system
of fibres to guide movements
on vesicles and other
organelles

16. Actin Filaments (Microfilaments)
• 2-stranded helical polymers of the protein actin
• Thin and flexible structure, diameter 5 - 9nm
• Generally unstable
• Can form stable structure when associating with
other actin-binding proteins
• Perform a variety of functions depending on the
protein it associated with

17. 2 main functions of Actin filaments
• Muscle contraction

18. 2. Cell locomotion
(“crawling”)
E.g. amoebae

19. Cell Cycle
• Duplication and division
• Essential mechanism by which all living things
reproduce
• Details vary from one organism to another,
occur at different times
• Interphase (G0, G1, S and G2 phase) , M phase
(mitosis) and C phase (cytokinesis)

20. Cell cycle control system
• Ensures that events of the cell cycle (DNA
replication, mitosis, etc) occur in a set
sequence and that each process has been
completed before the next begins
• Achieved by means of molecular brakes that
can stop the cycle at various checkpoints: G1,
G2, M (mitosis)

22. M phase (Mitosis)
• A process of nuclear division
• Replicated copies of a cell’s DNA are organised into
chromosomes
• Identical copies of the DNA are then divided equally
between 2 daughter cells
• Five stages: Prophase, Prometaphase, Metaphase,
Anaphase and Telophase

23. Prophase
• Replicated chromosomes consisting of 2
closely associated sister chromatids condense
• Nuclear envelope breaks down
• Spindle fibres form as microtubules grow out
of the centrioles that move to opposite ends
of the cell

24. Prometaphase
• Starts abruptly with the breakdown of the nuclear
envelope
• Chromosomes attach to spindle microtubules via
their kinetochores and undergo active movement

25. Metaphase
• Kinetochores of the chromosomes line up along
the equator of the cell, moved by the spindle
microtubules
• The spindle is now fully formed and the
microtubules attach to each sister chromatid

26. Anaphase
• Begins when the sister chromatids synchronously
separate
• Centromere holding sister chromatids together
divides
• Kinetochore microtubules get shorter and spindle
poles move apart, both contributing to
chromosome segregation

27. Telophase
• 2 groups of chromosomes reach the opposite poles of
the spindle
• As a new nuclear envelope starts to form around each
group of chromosomes, they uncoil and the spindle
disappears
• Division of the cytoplasm begins with the assembly of
the contractile ring

28. C phase (cytokinesis)
• Division of cytoplasm and organelles
• Cytoplasm is divided into 2 by a contractile ring of
actin and myosin filaments
• Cleavage furrow forms by action of contractile ring
• Causes a pinch in the cell to create 2 daughters,
each with a nucleus

29. Meiosis I (reduction division)

30. Meiosis II (separation division)

31. Difference between Mitosis and Meiosis
Mitosis Meiosis
Occurs in somatic (body) cells Occurs only in reproductive (sex) cells
Diploid (2n) Haploid (n)
2 daughter cells (diploid) 4 daughter cells (haploid)
One cell division Two cell divisions
Genetically identical Genetically different

32. DNA Replication
• A process where DNA duplicates itself during
interphase
• Also called semi conservative replication
– Half of parent molecule retained by each daughter
molecule

33. Meet the proteins!
DNA Ligase:
Helicase: Joins the gaps
DNA Polymerase III: Single-strand DNA
Uses energy from between newly
Core replication Binding Protein:
ATP hydrolysis to synthesised DNA
enzyme of the cell Binds to single-
unwind DNA (Okazaki)
stranded DNA
fragments
DNA Polymerase
Sliding Clamp: DNA Primase: Removes the RNA
Beta subunit of DNA An RNA polymers that primer and
Polymerase III; encircles generates a short RNA replaces it with
and slides along the DNA primer DNA
(oligoribonucleotide)

34. Process of DNA replication
http://www.mcb.harvard.edu/losick/images/trombonefinald.swf

35. Alcohol metabolism causes DNA
damage and triggers a breast cancer-
related DNA damage response
• Ethanol is carcinogenic to human cells at
several sites in the body
• Alcohol metabolism product, acetaldehyde
causes DNA damage, chromosomal
abnormalities and acts as an animal
carcinogen
• Acetaldehyde acetate (relatively harmless)
• By enzyme aldehyde dehydrogenase2 (ALDH2)

36. • 30% of East Asians are unable to metabolise
alcohol to acetate due to a genetic variant in
the ALDH2 gene
• Increased risk of oesophageal cancer from
alcohol consumption
• findings show cells responded to DNA damage
by activating Fanconi anemia-breast cancer
(FA-BRCA) network –protects against breast
cancer

38. Bibliography
• Albert, B. et al., 2010. Essential Cell biology. 3rd ed. New York, NY: Garland
Science.
• Becker,W.M., Lewis,J.K. and Hardin,J., 2006. The World Of The Cell. 6th ed. San
Francisco, CA: Pearson Education.
• Alcoholism: Clinical & Experimental Research (2011, September 15). Alcohol
metabolism causes DNA damage and triggers a breast cancer-related DNA
damage response.ScienceDaily. Retrieved November 29, 2011, from
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39. •
Photo Credits
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40. Photo Credits
• http://www.sivabio.50webs.com/mus.htm
• http://www.cytochemistry.net/cell-biology/actin_filaments_intro.htm
• http://www.mcb.harvard.edu/losick/images/trombonefinald.swf
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