Transcript 1415Unit1PowerPnt

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Human Genetics: concepts and applications
6th edition
Ricki Lewis
Genetics : Unit 1
Cell Cycle and
Cancer
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•
A.
B.
C.
D.
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Where would be the best place to find lipids
in the cell?
Membranes
Nucleus
Ribosome
Endoplasmic reticulum
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•
A.
B.
C.
D.
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Which of the following are the four major
groups of macromolecules?
Nucleus, ribosome, cytoplasm, vacuole
Protein, lipid, carbohydrate, nucleic acid
Ionic, covalent, hydrogen, divalent
Sugar, phosphate, nitrogen, base
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Chemical Constituents of Cells
• The human body is composed of trillions of
cells
• Cells are constructed from numerous small
molecules and macromolecules.
– These include carbohydrates (simple
sugars and polysaccharides), amino acids
and proteins, lipids (fats and oils), and
nucleic acids (nucleotides, DNA, RNA).
– Enzymes are proteins that catalyze
biochemical reactions that occur in the cell.
1-4
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• Proteome: set of proteins that a particular cell
type can produce.
• Expression of different subsets of genes in
different cells (and therefore production of
different proteomes) gives rise to over 260
specialized cell types.
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Cell Graffiti
• You and a partner will sketch a cell. A
detailed cell that includes all of the major
organelles. As well as the function of the
organelles. You should also be able to
describe how the organelles interact.
• Make sure you include a small part of your
membrane in extreme detail, including
showing the lipids within the bilayer.
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Organelles
• Organelles represent the compartments in the cell
and are involved in a variety of functions
– The nucleus (storehouse of majority of DNA in
the cell) has a double membrane and nuclear
pores, which allow macromolecular traffic in and
out of the nucleus.
– The rough endoplasmic reticulum (ER), smooth
ER, and Golgi body function as a membrane
network for the synthesis of proteins and lipids
• targeted for delivery to the plasma
membrane, organelles, or for secretion
• Secretions bud off in vesicles and leave cell
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– A mitochondrion has a double membrane
whose inner folds carry enzymes that
catalyze reactions that extract energy from
nutrients; also contains small amounts of
DNA. (The chloroplast in plant cells also
contains a small amount of DNA)
– Lysosomes contain enzymes that degrade
cellular debris.
– Peroxisomes house enzymes that detoxify
certain substances, break down lipids, and
synthesize bile acids.
1-8
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1-9
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1-10
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The Cell Cycle
• The cell cycle consists of interphase, when a cell is not
dividing, and mitosis.
– G1 phase of interphase: proteins, lipids, and
carbohydrates are produced
– S phase of interphase: DNA and proteins are made
– G2 of interphase : more proteins are produced;
replicated chromosomes have two sister chromatids
attached at their centromeres
• The cell cycle is tightly controlled and regulated at
several "checkpoints.“
• Non-dividing cells may become arrested during
interphase and enter a quiescent phase (G0).
1-11
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1-12
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Cell cycle control
Proteins called checkpoint proteins monitor
progression through the cell cycle.
1-13
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Control of Cell Cycle Game
1-14
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Replication of chromosomes
• Replication is the process
of duplicating a
chromosome
• Occurs prior to division in
S phase of the cell cycle
• Replicated copies are
called sister chromatids
• Held together at
centromere
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Control of Mitosis
• A cellular clock that limits the number of
divisions is based on shrinking telomeres.
• Crowding, hormones, and growth factors are
extracellular influences on mitosis.
• Within cells, kinases and cyclins activate the
genes whose products carry out mitosis
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Mitosis
• Purpose: to make copies of cells and their DNA
• Replicated chromosomes align at the metaphase
plate.
• Sister chromatids separate and move to opposite
poles
• Nuclear membranes form around each new
nucleus.
• Division of cytoplasm or cytokinesis occurs.
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Prophase
• Replicated chromosomes
condense.
• Microtubules organize into
a spindle
• Nuclear membrane breaks
down
• Centrioles split and move
toward opposite poles of
the cell
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1-19
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Metaphase
• Chromosomes line up
on the metaphase
plate.
• Spindle microtubules
are attached to
centromeres of
chromosomes.
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Anaphase
• Centromeres of sister
chromatids separate
• Chromosomes move to
opposite ends of the
cell
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Telophase
• Chromosomes reach
poles of cell, diffuse into
chromatin
• Nuclear membranes
reform
• Spindle disappears
• Division of cytoplasm
begins (cytokinesis)
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1-23
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Cytokinesis
• Cell pinches in the middle and
the two new cells separate
• Cytokinesis is part of the M
phase of the cell cycle, but
usually considered separate
from mitosis; process begins
during telophase and may
continue after telophase is
complete
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Apoptosis
• Mitosis (cell division) and apoptosis (cell death)
are continuous processes that occur in a series of
steps and are both initiated by signals in the
extracellular environment
• The balance between cell division and death
maintains tissues in growth, development, and
repair
• In prenatal development, coordination of these
processes sculpts body form. After birth, mitosis
and apoptosis protect and maintain the body.
• Disruption of the balance between cell division
and cell death can lead to cancer or other
disorders.
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Apoptosis
Programmed cell death is part of normal development
chicken
embryo
Death receptor binds signal molecule.
Capase enzymes destroy proteins.
Cells fragment.
Phagocytes engulf cell remnants.
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Different amounts of apoptosis
create feet with digits versus
webbing.
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Cancer
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•
Cancer is a group of diseases caused by
loss of cell cycle control.
•
Cancer is associated with abnormal
uncontrolled cell growth.
•
Carcinogens are substances which cause
cancer by mutating DNA.
•
Many genes that can mutate to cause
cancer control the cell cycle or DNA
maintenance (repair).
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Origin of cancer
• Cancer begins from the growth of a single abnormal cell.
• A mutation occurs allowing a cell to undergo cell division
when it would not normally divide.
• Division produces more abnormal cells.
• Mutations can occur:
• In somatic cells => sporadic cancer only affecting the
individual
• In germline cells => mutations that are inherited
• Germline mutations usually require second somatic
mutation also.
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Germline versus sporadic
cancer
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Telomeres affect the cell cycle
Telomerase is the protein and enzyme complex that adds
telomere sequences to the ends of chromosomes.
Presence of telomerase and telomeres allows cells to
pass a cell cycle checkpoint and divide.
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Telomeres affect the cell cycle
When telomerase is absent, telomeres are not added.
Lack of telomeres signals cessation of cell division.
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Cancer can progress slowly
over years
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Types of cancer genes
Type of gene
Normal function
Mutated function Types of proteins
Oncogene
Promotes
division
Promotes
Growth factors
division abnormal time or
cell type
Tumor
suppressor
gene
Suppresses cell
division
Fails to suppress Checkpoint
division
molecules
DNA repair
gene
mutation
Repair DNA
mutations
Fail to repair
DNA mutations
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Enzymes for
mismatch or
excision repair
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Characteristics of cancer cells
• Divide continually (given space and nutrients)
• Heritable mutations: cells with mutations have
daughter cells which inherit the same
mutations.
• Dedifferentiated: cells lose their specialized
identity
• Different appearance: reflects
dedifferentiation
• Lack contact inhibition: will divide in a crowd
of cells and pile on top of each other
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• Induce angiogenesis (local blood vessel
formation)
• Increased mutation rate
• Invasive: squeeze into any space
available
• Metastasize: cells move to new location
in the body
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Oncogenes
• Proto-oncogenes are normal versions of genes which
promote cell division.
• Expression at the wrong time or in the wrong cell type
leads to cell division and cancer.
• Proto-oncogenes are called oncogenes in their mutated
form.
• One copy of an oncogenic mutation is sufficient to promote
cell division.
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Tumor suppressor genes
• Cancer can be caused by loss of genes that inhibit
cell division.
• Tumor suppressor genes normally stop a cell from
dividing.
• Mutation of both copies of a tumor suppressor gene
is usually required to allow cell division.
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p53 coordinates cell cycle
regulation
• p53 acts as a cell cycle protein which determines if a
cell has repaired DNA damage. If damage cannot be
repaired, p53 can induce apoptosis.
• More that 50% of human cancers involve an
abnormal p53 gene.
• Rare inherited mutations in the p53 gene cause a
disease called Li-Fraumeni syndrome in which family
members have many different types of cancer at
early ages.
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BRCA1, a breast cancer susceptibility
gene
• Within families a mutation in BRCA1 leads
to breast cancer susceptibility, inherited as
a dominant trait.
• One mutation in the BRCA1 gene is inherited.
• Tumors occur when people acquire a second
mutation in the normal allele of BRCA1.
• Lack of any functional BRCA1 leads to cancer
cells.
• At the level of the cell, BRCA1 acts in a
recessive manner.
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Cancer treatments for breast
cancer
Strategy
Examples
Remove cancerous
tissue
Surgery
Destroy cancerous
tissue
Use phenotype to
select drug
Use genotype to
select drug
Genomic level
Radiation or chemotherapy to kill
dividing cells
Estrogen receptor positive women
take tamoxifen
Her-2/neu positive cancers
targeted with herceptin MAb
Gene expression profile on DNA
microarray to guide drug choice
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Environment impacts cancer
• Exposure to carcinogens
• Carcinogens in tobacco smoke are correlated
with lung cancer incidence.
• Exposure to radiation
• Burns from overexposure to sunlight can
cause skin cancer.
• Variation in diet
• Fatty diets are correlated with increased
estrogen and increased breast cancer.
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Cruciferous vegetables can
lower cancer risk
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