COVER SLIDE

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COVER SLIDE
Repairing DNA
Our best defense against cancer
UCRL-PRES-220245
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COVER SLIDE
John Hinz, Ph.D. Research Scientist, LLNL
With assistance from Salustra Urbin, Biomedical
Technician, LLNL Kirk Brown, Science Dept.
Chair, Tracy High School
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Overview Cells to Cancer
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We are made of trillions of cells
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Cells have many parts
Cell components Plasma Membrane Cytoplasm Organel
les Nucleus DNA
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Cells serve many functions

• Every cell in you body has a job
• Cells work together to form tissues and organs

Examples Muscle (Moving) Lung (Breathing) Nerve
(Thinking) Skin (Protecting)
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Proteins allow the cell to do its job
A cell does its job based on the proteins in makes
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DNA chromosomes to base pairs
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DNA (Deoxyribonucleic acid)
-Each nucleotide has a chemical base (A, T, G, or
C)
-DNA has two opposing strands, and bases on one
strand partner with bases on the other strand
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DNA forms a double helix
The opposing strands wind around each other,
forming a double helix
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Chromosomes are long DNA molecules

• Nucleotides are arranged in long molecules called
  chromosomes
• Human cells have 46 chromosomes

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DNA/CHROMOSOMES
Human Cell
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DNA/CHROMOSOMES
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Genes encode the proteins
Genes are the regions of a chromosome that are
read to make the proteins for the cell. Each
gene encodes a cell protein
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GENES to PROTEINS
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The order of the DNA bases determines the protein
Every cell has all the chromosomes all the genes
Not all cells read every gene, they only make the
proteins required for their job.
The specific order of the bases (sequence) in a
gene is important for making the protein
correctly.
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Mutations Permanent changes in the DNA sequence

• Two general types of mutations
• 1. Base substitutions changes in the DNA
  sequence
• 2. Chromosomal rearrangements exchanges of
  large regions of DNA

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Base Substitutions change the DNA sequence
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DNA sequence changes can change proteins
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Chromosomal rearrangements
Loosing genes Moving genes
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Tumor cell karyotype
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Two general causes of mutations

• 1. Mistakes by a DNA polymerase
• a. Polymerase Errors
• b. Polymerase Problems
• 2. Breaks in the DNA

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DNA polymerases copy the DNA
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DNA polymerases copy the DNA
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DNA polymerases make mistakes
Sometimes polymerases put in the wrong nucleotide
Mutation?
Base substitution
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DNA polymerases make mistakes
Damaged bases are hard to read, causing
polymerase errors
Mutation?
Base substitution
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DNA polymerases make mistakes
Sometimes the polymerase complex collapses
Mutation?
Chromosomal rearrangement
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Sometimes the helix just breaks
Mutation?
Chromosomal rearrangements
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DNA is a reactive molecule

• DNA is a molecule subjected to chemical reactions
• Chemical modification of bases DNA damage
• Damage occurs spontaneously or from exogenous
  agents

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DNA repair finds and removes DNA damage
The processes used by the cell to correct
polymerase errors and to repair chemical or
physical damage to the DNA before it causes a
mutation or cell death. Performed by groups of
proteins that coordinate their activities to
detect and correct the problem.
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Mismatch Repair

• The proof-reading repair system used to correct
  polymerase errors

Mutations prevented?
Base substitutions
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Excision Repair
Removes damaged bases and replaces them before a
DNA polymerase stumbles through them.
Mutations prevented?
Base substitutions Chromosomal rearrangement
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Break Repair
Repair mechanisms used to attach broken ends of
DNA to restore chromosome integrity.
Mutations prevented?
Chromosomal rearrangements
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How does DNA repair protect us from Cancer?

• Prevents mutations in genes that encode proteins
  that can prevent cancer or promote cancer
• Tumor Suppressor genes
• Oncogenes

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Tumor suppressor genes control cell growth
Encode proteins that act to suppress cell growth,
respond to signals outside the cell, maintain
DNA, and repair damage.
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Oncogenes support cell growth
Onco- tumor (Greek) Encode proteins that
control cell growth (proto-oncogenes)
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Cells require a balance of tumor suppressor and
oncogene activity
Tumor Suppressors
Oncogenes
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Too many tumor suppressor activities can lead to
cell growth arrest or death

• Slow down
• Obey
• Stay put
• Repair carefully

Oncogenes
Tumor Suppressors
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Too much oncogene activity can lead to
increased/uncontrolled cell division
Grow! Grow! Grow! Grow!
Tumor Suppressors
Oncogenes
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Selection allows tumor formation
Tumor (Swelling, Latin) Abnormal mass of cells
Mutations that inactivate tumor suppressors or
over-activate oncogenes give cells a selective
advantage
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Cancer
Cancer A class of diseases characterized by the
uncontrolled division of cells Carcinos
(Greek) Crab Referring to the appearance
of malignant tumor Later translated into
the Latin Cancer Oncology Study of
cancer Oncos (Greek) Swelling or Tumor
-ology (Greek) A branch of learning
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Tumors can be invasive or metastatic
Invasive tumors have mutations that allow cells
to press themselves into adjacent tissues
Metastatic tumors have mutations that allow cells
to grow at distant sites
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How DNA repair prevents cancer
DNA damage is continuous and stochastic
Most damage is repaired
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Audience tumor drill 1Spontaneous tumors
You are the cells! Will any of you become tumors?
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Ultraviolet light causes cancer
Cells from which tissues become tumors?
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Audience tumor drill 2Sunbathing-induced tumors
You are the cells! Will any of you become tumors?
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Smoking causes cancer
Cells from which tissues become tumors?
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Audience tumor drill 3Smoking-induced tumors
You are the cells! Will any of you become tumors?
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Important Cancer Facts
1 cause of death in 2005 (2 is heart
disease) Most common cancer in US Cancer that
causes the most deaths 30 of all cancer
deaths caused by tobacco use 33 of cancer
deaths are related to diet and exercise
Skin
Lung
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Cancer rates
Incidence
Mortality
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What can you do to prevent cancer?
Dont smoke or use tobacco products Wear
sunscreen, and avoid UV exposure Good diet
(Fruits Veggies) Regular exercise Medical
exams/self exams
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Cancer information Websites
American Cancer Society http//www.cancer.org Na
tional Cancer Institute http//www.cancer.gov/ S
urveillance Epidemiology and End Results
(Statistics) http//seer.cancer.gov/ The Skin
Cancer Foundation http//www.skincancer.org/ Lun
g Cancer Foundation http//www.lungcancer.org/ H
arvard Center for Cancer Prevention http//www.hs
ph.harvard.edu/cancer/
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The future of cancer research

• What we need to understand
• Prevention (causes of damage, cell growth, DNA
  repair)
• Targeting of tumor cells (How are they different,
  weaknesses)
• Managing the disease

Who we need to do this The next generation of
cancer researchers You!
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How to become a Cancer Researcher
College (bachelors degree) Subjects
(majors/minors) Biology, Chemistry, Physics,
Math, Computer sciences
Research experience Summer student opportunities,
hospital /lab volunteer work

• Graduate School (Ph.D.)
• Research fundamental aspects of science
• Test own ideas to explore undiscovered principles

• Medical School (M.D.)
• Apply research to help patients
• Perform human experiments (clinical trials)

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Salustra
John
Cells
Toxic Fumes