the cytoskeletal system, cell cycle and dna(project)
TRANSCRIPT
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The cytoskeletal system, cell cycle and DNA replication
Hilary MokYolande Leong
BMS/1M02Cheesecake!
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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
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Functions of the cytoskeleton• Establishes cell shape• Provides mechanical
strength• Locomotion• Chromosome separation
in mitosis and meiosis
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Components of cytoskeletal system
1. Intermediate Filaments2. Microtubules3. 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
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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
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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)
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Categories of IF
Intermediate Filaments
Cytoplasmic
KeratinsVimentin and
Vimentin-related filaments
Neurofilaments
Nuclear
Nuclear Lamins
In (mostly) epithelial cells
In connective tissue, muscle cells and glial cells
In nerve cells In all animal cells
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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
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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
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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
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• 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
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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
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Axonemal microtubules• Highly organised, stable microtubules in
specific subcellular structure associated with cellular movements (E.g. cilia, flagella)
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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
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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
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2 main functions of Actin filaments
• Muscle contraction
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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)
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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)
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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
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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
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Prometaphase• Starts abruptly with the breakdown of the nuclear
envelope• Chromosomes attach to spindle microtubules via
their kinetochores and undergo active movement
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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
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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
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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
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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
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Meiosis I (reduction division)
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Meiosis II (separation division)
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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
Difference between Mitosis and Meiosis
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DNA Replication
• A process where DNA duplicates itself during interphase
• Also called semi conservative replication– Half of parent molecule retained by each daughter
molecule
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Meet the proteins!Helicase:Uses energy from ATP hydrolysis to unwind DNA
DNA Polymerase III:Core replication enzyme of the cell
Sliding Clamp:Beta subunit of DNA Polymerase III; encircles and slides along the DNA
Single-strand DNA Binding Protein:Binds to single-stranded DNA
DNA Primase:An RNA polymers that generates a short RNA primer (oligoribonucleotide)
DNA Polymerase Removes the RNA primer and replaces it with DNA
DNA Ligase:Joins the gaps between newly synthesised DNA (Okazaki)fragments
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Process of DNA replication
http://www.mcb.harvard.edu/losick/images/trombonefinald.swf
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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)
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• 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
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Thank You!
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