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Mutations and
Cancer
Vocabulary
• Mutation
• Mutagen
• Cancer
• Carcinogen
• Tumor (benign vs. malignant)
• Metastasis
• Oncogene vs. Proto-oncogene
• Tumor-suppressor gene
• Checkpoint proteins
3
4
5
MITOSIS
MITOSIS
FERTILIZATION
MEIOSIS MEIOSIS
Gametes
(sperm and egg cells)
Zygote
(fertilized egg)
New cells (and organisms) need new
DNA
Mutation=
heritable change in genetic material
Point mutations
Simplified examples
How can a mutation be ‘silent’?
Does the mutation increase or decrease
functionality of the final product?
Sickle cell disease, from a point
mutation .
A
TRANSCRIPTION TRANSCRIPTION
TRANSLATIONTRANSLATION
Original allele
Protein
DNA
Mutated allele
Two alleles of the gene
3′ 5′ 3′ 5′
5′ 3′
mRNA
Two versions of the protein
Functional Defective
3′5′
Figure 7.27
T T T TA A A A A AAA A A A A A A A
AAA AU U UU U U U U U U U U UCC C G G GGGGG
G G G G C C CCC C
lle lle lle lle GlyGly ValValPhe
Location
matters!
G2 checkpoint
• Has all DNA replicated?
• Can damaged DNA be repaired?
• Is spindle-making machinery
in place?
Metaphase
checkpoint
• Do kinetochores
attach to spindle?
• Are chromosomes
aligned down
equator?
S phase checkpoint
• Is DNA replicating
correctly?
S phase
(DNA replication)
G2 phase
(additional growth
and preparation
for division)
G1 phase
(normal cell function
and cell growth)
G1 checkpoint
• Is DNA damaged?
G0 phase
(nondividing)
Regulation of
Cell Division
Growth Factors
• Signaling molecule in
animals, promotes
cell division
• Example: Dog saliva,
wound-licking
Checkpoints
• Protein sensors
determine if cell is
OK to continue
through the cell
cycle
Apoptosis=
programmed cell
death
(it’s a good thing!)
MITOSIS
MITOSIS
FERTILIZATION
MEIOSIS MEIOSIS
Gametes
(sperm and egg cells)
Figure 8.1
Zygote
(fertilized egg)
DNA RNA Protein
If something goes wrong…
DNA polymerase adds DNA
nucleotides to the RNA
primer. Proofreading activity
checks and replaces
incorrect bases just added.
Leading (continuous)
strand synthesis continues
in a 5′ to 3′ direction.
Helicase separates strands.
Binding proteins prevent
single strands from rejoining.
Primase makes a short stretch
of RNA on the DNA template.
Overall direction of replication
Discontinuous
synthesis of the lagging
strand produces
Okazaki fragments.
After RNA primer is replaced with DNA,
ligase seals the sugar–phosphate backbone.
Steps in DNA replication
RNA primers
New DNA
strands
Okazaki
fragment
Leading strand
Lagging strand
3’
3’
3’
3’
3’
3’
3’
3’
3’
3’
3’
3’ 3’
3’
3’
3’
3’
3’
5’
5’
5’
5’
5’
5’
5’
5’
5’
5’
5’
5’
5’5’
5’
5’
5’5’
…proteins of DNA
Replication.
…proteins of gene expression.
…proteins of cell division.
Cancer=
out of control
cell division
Typical progression of cancer.
Malignant cells can "seed" new
tumors throughout the body.
Blood
vessel
Malignant
tumor
Benign
tumor
Capsule of connective tissue
keeps tumor from spreading.
Lymph
vessel
Lymph
vessel
a. Benign tumor b. Malignant tumor
Metastasis
Blood
vesselsNew
tumor
New
tumor
Lymph
vessel
Capsule
Progression of lung cancer.
Tumor takes up critical
surface area for gas
exchange.
Note invasion of underlying
tissue by cancerous cells.
Cancer genes?
Two major categories
“Cancer Genes” = mutated versions
of normal genes
Oncogenes
• Overactivity of gene
• Non-mutated form
known as proto-
oncogene
• Increase cell division
• Gas pedal
Tumor-suppressor Genes
• Mutations cause loss of
activity
• Normal function,
decrease cell division,
promote apoptosis
• Brake pedal
Proto-oncogene Tumor suppressor gene
Mutated or silenced
proteins
block cancer
development.
Proteins absent or
fail to block cancer
Development.
proteins
accelerate cell cycle.
Normal
Normal proteins
stimulate cell
division.
Oncogene
Cancer cells No CancerNormal cells
Mutated or overly activeNormal
Normal cell
Think about the consequences of
mutated ‘cancer genes’
• Gas pedal stuck “ON” but brakes still working
• Brakes not working but can still take foot off the gas
pedal
• Gas pedal stuck ”ON” AND brakes not working!!
Potential Oncogenes
Tumor-
suppressor genes
To avoid or reduce the risk of cancer
Eat a healthy diet, low in saturated
fat and rich in fruits and vegetables
Avoid UV radiation
from sunlight and
tanning beds.
Stop using
tobacco,
or better yet,
never start.
Use self tests
and medical exams
for early detection.
Use condoms to
avoid exposure
to viruses known
to cause cancer.
Get regular
vigorous
exercise.
Avoid obesity:
Cancer risk factors
Carcinogens AND Genetics

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Mutations and Cancer

  • 2. Vocabulary • Mutation • Mutagen • Cancer • Carcinogen • Tumor (benign vs. malignant) • Metastasis • Oncogene vs. Proto-oncogene • Tumor-suppressor gene • Checkpoint proteins
  • 3. 3
  • 4. 4
  • 5. 5
  • 6. MITOSIS MITOSIS FERTILIZATION MEIOSIS MEIOSIS Gametes (sperm and egg cells) Zygote (fertilized egg) New cells (and organisms) need new DNA
  • 7.
  • 8. Mutation= heritable change in genetic material
  • 10. How can a mutation be ‘silent’?
  • 11. Does the mutation increase or decrease functionality of the final product?
  • 12. Sickle cell disease, from a point mutation .
  • 13. A TRANSCRIPTION TRANSCRIPTION TRANSLATIONTRANSLATION Original allele Protein DNA Mutated allele Two alleles of the gene 3′ 5′ 3′ 5′ 5′ 3′ mRNA Two versions of the protein Functional Defective 3′5′ Figure 7.27 T T T TA A A A A AAA A A A A A A A AAA AU U UU U U U U U U U U UCC C G G GGGGG G G G G C C CCC C lle lle lle lle GlyGly ValValPhe
  • 14.
  • 15.
  • 17. G2 checkpoint • Has all DNA replicated? • Can damaged DNA be repaired? • Is spindle-making machinery in place? Metaphase checkpoint • Do kinetochores attach to spindle? • Are chromosomes aligned down equator? S phase checkpoint • Is DNA replicating correctly? S phase (DNA replication) G2 phase (additional growth and preparation for division) G1 phase (normal cell function and cell growth) G1 checkpoint • Is DNA damaged? G0 phase (nondividing) Regulation of Cell Division Growth Factors • Signaling molecule in animals, promotes cell division • Example: Dog saliva, wound-licking Checkpoints • Protein sensors determine if cell is OK to continue through the cell cycle
  • 19. MITOSIS MITOSIS FERTILIZATION MEIOSIS MEIOSIS Gametes (sperm and egg cells) Figure 8.1 Zygote (fertilized egg)
  • 20. DNA RNA Protein If something goes wrong…
  • 21. DNA polymerase adds DNA nucleotides to the RNA primer. Proofreading activity checks and replaces incorrect bases just added. Leading (continuous) strand synthesis continues in a 5′ to 3′ direction. Helicase separates strands. Binding proteins prevent single strands from rejoining. Primase makes a short stretch of RNA on the DNA template. Overall direction of replication Discontinuous synthesis of the lagging strand produces Okazaki fragments. After RNA primer is replaced with DNA, ligase seals the sugar–phosphate backbone. Steps in DNA replication RNA primers New DNA strands Okazaki fragment Leading strand Lagging strand 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’5’ 5’ 5’ 5’5’ …proteins of DNA Replication.
  • 22. …proteins of gene expression.
  • 23. …proteins of cell division.
  • 25.
  • 27.
  • 28. Malignant cells can "seed" new tumors throughout the body. Blood vessel Malignant tumor Benign tumor Capsule of connective tissue keeps tumor from spreading. Lymph vessel Lymph vessel a. Benign tumor b. Malignant tumor Metastasis Blood vesselsNew tumor New tumor Lymph vessel Capsule
  • 29.
  • 30. Progression of lung cancer. Tumor takes up critical surface area for gas exchange. Note invasion of underlying tissue by cancerous cells.
  • 32. “Cancer Genes” = mutated versions of normal genes Oncogenes • Overactivity of gene • Non-mutated form known as proto- oncogene • Increase cell division • Gas pedal Tumor-suppressor Genes • Mutations cause loss of activity • Normal function, decrease cell division, promote apoptosis • Brake pedal
  • 33. Proto-oncogene Tumor suppressor gene Mutated or silenced proteins block cancer development. Proteins absent or fail to block cancer Development. proteins accelerate cell cycle. Normal Normal proteins stimulate cell division. Oncogene Cancer cells No CancerNormal cells Mutated or overly activeNormal Normal cell
  • 34.
  • 35. Think about the consequences of mutated ‘cancer genes’ • Gas pedal stuck “ON” but brakes still working • Brakes not working but can still take foot off the gas pedal • Gas pedal stuck ”ON” AND brakes not working!!
  • 38. To avoid or reduce the risk of cancer Eat a healthy diet, low in saturated fat and rich in fruits and vegetables Avoid UV radiation from sunlight and tanning beds. Stop using tobacco, or better yet, never start. Use self tests and medical exams for early detection. Use condoms to avoid exposure to viruses known to cause cancer. Get regular vigorous exercise. Avoid obesity: Cancer risk factors Carcinogens AND Genetics