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Unit 4: Cell Cycle and DNA
Concepts 9 and 10
Lecture 1
Cell Division and the Cell Cycle
The need for cell division
• Cells arise from existing cells.
• Each cell receives genetic instructions from
its parent cell.
• Before cell division occurs, the cell
replications, or copies, all of its DNA.
– Each daughter cell receives one complete set of
genetic information.
– Allows life to continue.
http://en.wikipedia.org/wiki/File:Kinetochore.jpg
Prokaryotic Cell
Reproduction
• Prokaryotes (including
Bacteria!) contain a single
circular DNA molecule.
• Prokaryotes reproduce
through binary fission.
• Binary Fission: Replication
of bacteria chromosomes
followed by distribution to
two asexual offspring.
http://en.wikipedia.org/wiki/Fission_(biology)
• Eukaryotic DNA is carried by
chromosomes.
– Made of DNA and proteins.
• Humans have 46 chromosomes.
– 2 Sets of 23
• Before cell division, each chromosome
is replicated.
– Each chromosome consists of two identical
“sister” chromatids.
– When the cell divides, the sister
chromatids separate from one another,
each going into one new cell.
– Centromere: Area where chromatids
attach.
• When a somatic cell contains two sets
of chromosomes, it is diploid (2n).
• When a cell contains only one set of
chromosomes, it is haploid (n).
Chromosomes
Sex Chromosomes
• Of the 23 pairs of chromosomes in human
somatic cells, 22 pairs are called
autosomes.
• Autosomes: chromosomes that are not a
sex chromosome.
• Sex Chromosomes: one pair of
chromosomes that determine the sex of
the individual.
– Sex chromosomes are referred to as X and Y.
The genes that cause an egg to develop into
a male are on the Y chromosome.
– In humans, male are XY and females are XX
– In some insects, there is no Y chromosome;
instead, females are XX and males are XO.
http://en.wikipedia.org/wiki/File:PAR.jpg
The Cell Cycle
• Cell Cycle: The series of events that cells go through
as they grow and divide.
– A cell grows, prepares for division, and divides to form two
daughter cells, each of which then begins the cycle again.
– The first three stages are
collectively called interphase.
• Four Phases:
– G1 Phase: Cell Growth
– S Phase: DNA Replication
– G2 Phase: Prepares for
Mitosis
– M Phase: Mitosis
and Cytokinesis
The Cell Cycle
1. Cell Growth (G1) Phase: When cells do most of their growing.
– Cells that are not dividing or preparing to divide remain in this
phase, but it is called G0!
2. DNA Replication (S) Phase: Chromosomes are replicated and the
synthesis of DNA molecules takes place.
3. Preparation for Mitosis (G2) Phase: Organelles and molecules
required for division are produced.
4. Mitosis (M) Phase: Process during cell division in which the nucleus
is divided into two nuclei, each with the same number of
chromosomes as the original cell.
Mitosis
1. Prophase: Stage of mitosis when chromosomes become visible.
Centrioles move to opposite sides of the nucleus. Spindles form.
Nuclear envelopes break down.
2. Metaphase: Stage of mitosis when the chromosomes line up across
the center of the cell.
3. Anaphase: Stage of mitosis when sister chromatids separate into
individual chromosomes and are moved apart.
4. Telophase: Stage of mitosis when chromosomes gather at opposite
ends of the cell and lose their distinct shapes. Two nuclear envelopes
will form.
Mitosis
Cytokinesis
• Cytokinesis: The division of the cytoplasm.
– In animals, the cell is pinched in two nearly equal parts,
each with its own nucleus and organelles.
– In plants, a cell plate forms midway and gradually
develops into a separating membrane.
Lecture 2
Cell Cycle and Cancer
Controls on Cell Division
• When cells dividing on a nutrient broth petri
dish come into contact with other cells, they
stop growing.
• The response in your body is similar if you cut
yourself and your skin heals.
Cell Cycle Regulators
• Cyclin: Proteins involved in cell cycle regulation.
– Regulate the timing of the cell cycle in eukaryotic
cells.
• Two types of regulator proteins.
– Internal Regulators: Proteins that respond to events
inside the cell.
• Example: Ensures that a cell does not enter mitosis until all
chromosomes are replicated.
– External Regulators: Proteins that respond to events
outside the cell.
• Example: Direct cells to speed up or slow down the cell
cycle.
Uncontrolled Cell Growth
• Cancer: A disorder in which some of the body’s own cells
lose the ability to control growth.
– Cancer cells do not respond to the signals that regulate the
growth of most cells.
• In cancer cells, control of the cell cycle is broken down.
– Sometimes internal regulators are not produced, some do not
respond to external regulators.
• Many cancer cells have a defect in the p53 gene which
normally halts the cell cycle until all chromosomes have
been properly replicated.
• Damaged or defective p53 genes cause the cells to lose the
information needed to respond to signals that would
normally control growth.
Cell Cycle and Cancer
• Cancer cells can go on dividing indefinitely in
culture if they are given nutrients; they are
immortal.
• The problem starts when a single cell undergoes
transformation; this is usually recognized by the
immune system.
• However, if the cell is not destroyed, it can form a
tumor.
– Some tumors cannot move sites, others can spread to
new tissues in a process called metastasis.
Lecture 3
DNA
Griffith’s Experiments
• When Griffith injected mice with disease causing bacteria, the
mice developed pneumonia and died.
• If mice were injected with harmless bacterial strain, they did
not get sick.
• Heat-killed deadly bacteria did not make mice sick.
• However, mixture of live harmless bacteria and heat-killed
deadly bacteria caused the mice to become sick and die.
• This process is called transformation; one strain of bacteria
had apparently been changed into another.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Avery’s Experiments
• So, what caused Griffith’s
transformation?
• Scientists wanted to
determine what molecule
caused transformation.
• Avery showed if they broke
down DNA, transformation
could not occur.
• These experiments allowed
scientists to know that DNA
was the material of
transformation.
Hershey-Chase Experiment
• Hershey and Chase used bacteriophages (viruses that infect
bacteria) to determine what viruses were adding to infect
cells.
• They marked phosphorus (because proteins contain almost
none) and sulfur (because DNA contains none) using
radioactive isotopes.
• All of the radioactivity in infected cells was from phosphorus,
indicating that the genetic material of the virus was DNA.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Purines and
Pyrimidines
• DNA is made of units
(monomers) called
nucleotides.
• Each nucleotide contains a
five-carbon sugar and a
phosphate group.
• Additionally, each nucleotide
contains a nitrogenous base.
There are four possible bases:
– Purines
• Adenine (A)
• Guanine (G)
– Pyrimidines
• Cytosine (C)
• Thymine (T)
Chargraff’s Rules
• Chargraff had discovered that the percentages of
Guanine and Cytosine are almost always equal.
• Similarly, the percentage of Adenine and Thymine
are almost always equal.
The Double Helix
• Rosalind Franklin used X-ray
diffraction to get information about
DNA structure.
• The X shape picture to the right tells
us that the strands in DNA are
twisted into a helix.
• Watson and Crick used Franklin’s
photo to determine the double helix
structure of DNA.
– Their model was a double helix in which
two strands of DNA twist around each
other.
Pairing Between Bases
• A purine on each strand (A or G) is always paired with a pyrimidine on the
other strand (C or T)
• A pairs with T and G pairs with C
• Two strands contain complementary base pairs—the sequence of bases on
one strand determines the sequence on the other strand.
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Chromosome Structure
• Eukaryotic DNA is very tightly packed into linear
chromosomes.
• Chromatin: Tightly packed DNA and protein.
– Consists of DNA tightly coiled around histone proteins to
form nucleosomes. Nucleosomes pack together to form
coils. Coils are then further folded to form supercoils.
Nucleosome
Chromosome
Supercoils
Coils
Histones
• During most of
DNA
the cell cycle,
double
the chromatin
helix
is dispersed in
the nucleus of
the cell and
the
chromosomes
are not visible.
Lecture 4
DNA Replication
DNA Replication
• Replication: The copying of DNA before cell division.
– The two strands of the double helix separate forming a
replication fork and produces two new complementary
strands using base pairing rules. Each strand serves as a
template for the new strand.
Original strand
New strand
DNA
polymerase
Growth
DNA polymerase
Growth
Replication fork
Replication fork
New strand
Original strand
Nitrogenous bases
Steps of DNA
Replication
• First, enzymes unzip the
double helix.
– DNA helicase
• DNA Polymerase: joins
individual nucleotides to
produce a DNA molecule;
also proofreads the new
strand.
– DNA replication is
semiconservative because
each new DNA molecule
consists of one old (blue)
and one new (yellow)
strand!
http://en.wikipedia.org/wiki/Directionality_(molecular_biology)
The Direction of Replication
• Replication occurs in the 5’ to 3’
direction.
• This refers to the carbon on the
sugar molecule in the sugarphosphate backbone.
• DNA strands run antiparallel,
meaning that the two DNA
strands of the double helix run
in opposite directions.
• This means when DNA is
replicated, it is done so in
opposite directions.
Replication
• Leading Strand: The DNA strand that is replicated without
interruption in the 5' to the 3' direction.
• Lagging Strand: The DNA strand that is replicated discontinuously in
the 5' to the 3' direction.
• Okazaki Fragment: Segments of DNA replicated on the lagging
strand.
Leading
strand
Overview
Origin of replication
Lagging
strand
Primer
Lagging
strand
Overall directions
of replication
Leading
strand
Lecture 5
RNA and Transcription
RNA and Protein
Synthesis
• Gene: Coded DNA
instructions that
control the
production of
proteins within
the cell.
– DNA is used to
make RNA
molecules which
contain coded
information used
to make proteins.
http://en.wikipedia.org/wiki/Central_dogma
RNA: How it differs from DNA
• Proteins are not built directly
from DNA.
• RNA is also involved.
• RNA=RiboNucleic Acid
• Three Differences between
DNA and RNA
– RNA is generally singled
stranded rather than double
stranded.
– RNA has ribose sugar rather
than deoxyribose sugar.
– RNA has Uracil (U) rather
than Thymine (T) bases. U
pairs with A.
http://en.wikipedia.org/wiki/RNA
Types of RNA
• Three main types of RNA
molecules are involved in
protein synthesis:
• Messenger RNA (mRNA):
Carry copies of
instructions for
assembling amino acids
into proteins.
• Ribosomal RNA (rRNA):
RNA that makes up part
of ribosome structure.
• Transfer RNA (tRNA):
Transfers each amino acid
to the ribosome as
specified by the mRNA.
http://en.wikipedia.org/wiki/File:MRNA-interaction.png
Transcription
• Transcription: copying part of DNA into a
complementary sequence of RNA.
• RNA Polymerase: Binds to DNA and separates the
strands. Then uses one strand of DNA as a template
to assemble nucleotides into a strand of RNA.
– Binds to regions of DNA known as promoters.
Adenine (BOTH)
Cytosine (BOTH
Guanine (BOTH)
Thymine (DNA ONLY)
Uracil (RNA ONLY)
Nuclear Envelope
RNA Polymerase
RNA Strand
DNA
Transfer of Information from DNA to RNA
• When RNA nucleotides are added during
transcription, they are linked together
with covalent bonds. As RNA Polymerase
moves down the strand, the strand of RNA
grows.
– Initiation, elongation, termination.
• In prokaryotes, transcription occurs in the
cytoplasm because prokaryotes have no
nucleus.
• In eukaryotes, transcription occurs in the
nucleus where the DNA is located.
• Occurs in the 5’ to 3’ direction.
• The strand of DNA used to make the RNA
is the “sense” strand, while the other
strand is called the “antisense” strand.
RNA Editing
•
The DNA of eukaryotes contains sequences that are not involved in coding for proteins.
– Introns are removed through a process called RNA splicing.
• Introns: Sequences of nucleotides that involved in coding for
proteins.
• Exons: Sequences of DNA that code for proteins.
– Expressed in the synthesis of proteins.
• Pre-mRNA is the initial produce of transcription; this pre-mRNA is then processed:
– A 5’ cap is added
– A poly-A tail is added to the 3’ end
Lecture 6
Translation and Protein Synthesis
The Genetic Code
• Polypeptides contain
combination of any or
all the different amino
acids.
• Every set of three letters
is a word that codes for
a single amino acid.
• Codon: Three
nucleotides that specific
a single amino acid to
be added to the
polypeptide.
Practice:
UCGCACGGU
UCG-CAC-GGU
Serine-Histidine-Glycine
Translation
• Translation: The decoding of an mRNA into a polypeptide chain.
• Translation begins when an mRNA in the cytoplasm attaches to a
ribosome.
• As each codon of the mRNA moves through the ribosome, the
proper amino acid is brought into the ribosome by tRNA.
• Each tRNA molecule carries only one kind of amino acid; it also
has three unpaired bases called an anticodon which complement
an mRNA codon.
Translation
Translation