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Chapter 3: Cells
• Plasma membrane: structure
• Plasma membrane: transport
• Resting membrane potential
• Cell-environment interactions
• Cytoplasm
• Nucleus
• Cell growth & reproduction
• Extracellular materials & developmental aspects
Department of Health, Nutrition, and Exercise Sciences
WCR
Cell cycle
From one cell division to the next
Interphase
Mitotic phase
G1 checkpoint
(restriction point)
S
Growth and DNA
synthesis
G1
Growth
M
G2
Growth and final
preparations for
division
G2 checkpoint
Copyright © 2010 Pearson Education, Inc.
Figure 3.31
Video
Molecular Visions of DNA
Narrated version at Walter & Eliza Hall Institute site. Animation of DNA replication and phase contrast
video of cell division.
http://www.wehi.edu.au/education/wehitv
Backup: Parent site:
Choose Molecular Visions of DNA.
Department of Health, Nutrition, and Exercise Sciences
WCR
DNA Replication
• DNA helices unwind from nucleosomes
• Each nucleotide strand serves as a template for building
a new complementary strand
• DNA polymerase makes the complementary strands
• End result: two DNA molecules formed from the original
Copyright © 2010 Pearson Education, Inc.
Chromosome
Free nucleotides
DNA polymerase
Old strand acts as a
template for synthesis
of new strand
Leading strand
Old DNA
Helicase unwinds
the double helix and
exposes the bases
Replication
fork
Adenine
Thymine
Cytosine
Guanine
DNA polymerase Old (template) strand
PLAY
Copyright © 2010 Pearson Education, Inc.
Two new strands (leading and lagging)
synthesized in opposite directions
Lagging
strand
Animation: DNA Replication
Figure 3.32
Cell Division
• Mitotic (M) phase of cell cycle
• Essential for body growth and tissue repair
• Does not occur in most mature neurons, skeletal and
cardiac myocytes
• Includes two distinct events
• Mitosis—nuclear division
• Cytokinesis—division of cytoplasm by cleavage furrow
PLAY
Copyright © 2010 Pearson Education, Inc.
Animation: Mitosis
Protein Synthesis
• DNA = master blueprint for protein synthesis
• Gene = segment of DNA with blueprint for one
polypeptide
• Polypeptide = polymer of amino acids; protein =
one or more polypeptides
• Each set of 3 nucleotide bases (triplet or codon)
specifies (codes for) an amino acid in the
polypeptide
PLAY
Animation: DNA and RNA
Copyright © 2010 Pearson Education, Inc.
Nuclear
envelope
Transcription
RNA Processing
DNA
Pre-mRNA
mRNA
Translation
Nuclear
pores
Ribosome
Polypeptide
Copyright © 2010 Pearson Education, Inc.
Figure 3.34
Three “classical” types of RNA
• Messenger RNA (mRNA)
• Carries instructions for building a polypeptide, from
gene in DNA to ribosomes in cytoplasm
• Ribosomal RNA (rRNA)
• A structural component of ribosomes that, along with
tRNA, helps translate message from mRNA
• Transfer RNAs (tRNAs)
• Bind to amino acids and pair with bases of codons of
mRNA at ribosome to begin process of protein
synthesis
Copyright © 2010 Pearson Education, Inc.
NYTimes Feb 7 2011
Fire & Mello: Nobel Prize, 2006, for discovery of RNA interference.
“Non-classical” types of RNA: regulatory
• Micro RNAs (miRNAs)
• Single-stranded, 21-33 nt, partly complementary to an
mRNA, usually down-regulates expression of mRNA’s
protein product
• Small interfering RNAs (siRNAs)
• Double-stranded, 20-25 nt, usually down-regulates
expression of complementary mRNA’s protein product;
lab-made versions being tested as treatments for
AIDS, AMD
• More types & roles being discovered
Copyright © 2010 Pearson Education, Inc.
Videos
Central Dogma, Part 1: Transcription (narrated version at WEHI.edu.au)
Central Dogma, Part 2: Translation (narrated version at WEHI.edu.au)
Hemoglobin & Sickle Cell Anemia
If there’s time:
No narration. Notes: Hb is a tetramer. Bright blue O2. Hb dark red; HbO2 bright red. HbS has one wrong
aa (green). HbS sticks together, forming intracellular rods.
http://www.wehi.edu.au/education/wehitv
Backup: Parent site:
Choose Central Dogma Part 1, then Central Dogma Part 2. Select Haemoglobin & Sickle Cell Anemia if time
allows.
Department of Health, Nutrition, and Exercise Sciences
WCR
Transcription
• Making mRNA from a gene on DNA
• mRNA complementary to corresponding DNA
• RNA polymerase
• Enzyme overseeing mRNA synthesis
• Unwinds DNA template, adds complementary RNA nucleotides,
joins them together
• mRNA detaches from DNA template, is further processed by
enzymes, exits nucleus & enter cytoplasm through nuclear pore
• Transcription factor
• Protein that binds to regulatory DNA near gene, usually enhances
transcription of gene
Copyright © 2010 Pearson Education, Inc.
RNA polymerase
Coding strand
DNA
Promoter
region
Template strand
Termination
signal
1 Initiation: With the help of transcription factors, RNA
polymerase binds to the promoter, pries apart the two DNA strands,
and initiates mRNA synthesis at the start point on the template strand.
mRNA
Template strand
Coding strand of DNA
2 Elongation: As the RNA polymerase moves along the template
Rewinding
of DNA
strand, elongating the mRNA transcript one base at a time, it unwinds
the DNA double helix before it and rewinds the double helix behind it.
mRNA transcript
RNA nucleotides
Direction of
transcription
mRNA
DNA-RNA hybrid region
Template
strand
RNA
polymerase
3 Termination: mRNA synthesis ends when the termination signal
is reached. RNA polymerase and the completed mRNA transcript are
released.
Unwinding
of DNA
The DNA-RNA hybrid: At any given moment, 16–18 base pairs of
DNA are unwound and the most recently made RNA is still bound to
DNA. This small region is called the DNA-RNA hybrid.
Completed mRNA transcript
RNA polymerase
Copyright © 2010 Pearson Education, Inc.
Figure 3.35
Translation
• Making a polypeptide (amino acid chain, usually a
protein) using mRNA “instructions”
• Involves mRNAs, tRNAs, rRNAs
• Small ribosomal subunit, then large, attach to mRNA
• tRNAs and their AAs, complementary to 1st & 2nd codons
on mRNA, attach to mRNA-ribosome complex
• Ribosome attaches the 2 AAs to each other, then moves
forward one codon on mRNA, releasing first tRNA
• Process repeats until reach stop codon – now
polypeptide is complete
Copyright © 2010 Pearson Education, Inc.
Nucleus
RNA polymerase
mRNA
Leu
Template
strand of
DNA
1 After mRNA synthesis in the
nucleus, mRNA leaves the nucleus
and attaches to a ribosome.
Energized by ATP, the correct amino
acid is attached to each species of
tRNA by aminoacyl-tRNA synthetase
enzyme.
Amino acid
Nuclear pore
tRNA
Nuclear
membrane
G A A
2 Translation begins as incoming
aminoacyl-tRNA recognizes the
complementary codon calling for
it at the A site on the ribosome. It
hydrogen-bonds to the codon via
its anticodon.
Released mRNA
Aminoacyl-tRNA
synthetase
Leu
3 As the ribosome moves along
the mRNA, and each codon is
read in sequence, a new amino
acid is added to the growing
protein chain and the tRNA in
the A site is translocated to the
P site.
Ile
tRNA “head”
bearing
anticodon
Pro
4 Once its amino acid is released
from the P site, tRNA is ratcheted
to the E site and then released to
reenter the cytoplasmic pool,
ready to be recharged with a new
amino acid. The polypeptide is
released when the stop codon is
read.
E
site
P
site
G G C
A
site
A U A C C G
C U U
Codon
15
Codon
17
Codon
16
Large
ribosomal
subunit
Small
ribosomal
subunit
Direction of
Portion of mRNA ribosome advance
already translated
Copyright © 2010 Pearson Education, Inc.
Figure 3.37
Role of Rough ER & Golgi in protein synthesis
• mRNA–ribosome complex finds and attaches to rough ER
• Forming protein enters ER
• Protein is enclosed in a vesicle for transport to Golgi
apparatus
• Sugar groups may be added to protein (glycosylation) in
RER and/or in Golgi
• Vesicles from Golgi carry finished proteins to cell surface
for incorporation into membrane or exocytosis
Copyright © 2010 Pearson Education, Inc.
1 The mRNA-ribosome complex is
directed to the rough ER by the SRP.
There the SRP binds to a receptor site.
ER signal
sequence
2 Once attached to the ER, the SRP is released
and the growing polypeptide snakes through the
ER membrane pore into the cisterna.
3 The signal sequence is clipped off by an
enzyme. As protein synthesis continues, sugar
groups may be added to the protein.
Ribosome
mRNA
Signal
Signal
recognition
sequence
particle Receptor site
removed
(SRP)
Growing
polypeptide
4 In this example, the completed
protein is released from the ribosome
and folds into its 3-D conformation,
a process aided by molecular chaperones.
Sugar
group
5 The protein is enclosed within a
protein (coatomer)-coated transport
vesicle. The transport vesicles make
their way to the Golgi apparatus,
where further processing of the
proteins occurs (see Figure 3.19).
Released
protein
Rough ER cisterna
Cytoplasm
Copyright © 2010 Pearson Education, Inc.
Transport vesicle
pinching off
Coatomer-coated
transport vesicle
Figure 3.39
Inner Life of a Cell
• Animation showing various aspects of cell function
including extracellular outer & inner membrane protein
interactions, cytoskeleton, translation, vesicular transport
• Leukocyte = WBC; endothelial cell = cell lining a blood
vessel
• Leukocyte extravasation = movement of leukocyte from
blood into surrounding tissue, as occurs at site of
inflammation
• Leukocyte is below & endothelial cell above, as if
leukocyte is rolling along “roof” of blood vessel
• High res animation
• Lower res, clip w/ music, other animations
College or Department name here
Sentinel node biopsy is a
technique which helps
determine if a cancer has
spread (metastasized), or is
contained locally. When a
cancer has been detected,
often the next step is to
find the lymph node closest
to the tumor site and
retrieve it for analysis. The
concept of the "sentinel"
node, or the first node to
drain the area of the
cancer, allows a more
accurate staging of the
cancer, and leaves
unaffected nodes behind to
continue the important job
of draining fluids. NYT
©2009.
The procedure involves the injection of a dye (sometimes mildly
radioactive) to pinpoint the lymph node which is closest to the
cancer site. Sentinel node biopsy is used to stage many kinds of
cancer, including lung and skin (melanoma). NYT ©2009.
KAAP
NYTimes Feb 8 2011
Axillary Dissection vs No
Axillary Dissection in
Women With Invasive
Breast Cancer and Sentinel
Node Metastasis: A
Randomized Clinical Trial.
Guiliano et al., JAMA 305:
569-575, 2011.
Context Sentinel lymph node dissection (SLND) accurately identifies
nodal metastasis of early breast cancer, but it is not clear whether
further nodal dissection affects survival.
Objective To determine the effects of complete axillary lymph node
dissection (ALND) on survival of patients with sentinel lymph node
(SLN) metastasis of breast cancer.
Conclusion Among patients with limited SLN metastatic breast cancer
treated with breast conservation and systemic therapy, the use of
SLND alone compared with ALND did not result in inferior survival.
KAAP
Extracellular Materials
• Body fluids (interstitial fluid, blood plasma, and
cerebrospinal fluid)
• Cellular secretions (intestinal and gastric fluids,
saliva, mucus, and serous fluids)
• Extracellular matrix (abundant jellylike mesh
containing proteins and polysaccharides in
contact with cells)
Copyright © 2010 Pearson Education, Inc.
Developmental Aspects of Cells
• Cells contain same DNA but are not identical
• Chemical signals in embryo channel cells into
specific developmental pathways by turning some
genes off
• Development of specific and distinctive features in
cells is called cell differentiation
• Elimination of excess, injured, or aged cells occurs
through programmed rapid cell death (apoptosis)
followed by phagocytosis
Copyright © 2010 Pearson Education, Inc.