# Presentation: 180055

## COVER SLIDE

**Repairing DNA**

**Our best defense against cancer**

- UCRL-PRES-220245

## 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**

## Overview: Cells to Cancer

## We are made of trillions of cells

## Cells have many parts

- _Cell components_
- Plasma Membrane
- Cytoplasm
- Organelles
- Nucleus
- DNA

## Cells serve many functions 

- 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)

## Proteins allow the cell to do its job

- A cell does its job based on the **proteins** in makes

## DNA: chromosomes to base pairs

## DNA (Deoxyribonucleic acid)

- -DNA has two opposing strands, and bases on one strand partner with bases on the other strand

- -Each nucleotide has a chemical **base** (A, T, G, or C)

## DNA forms a double helix

- The opposing strands wind around each other, forming a **double helix**

## Chromosomes are long DNA molecules

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

## DNA/CHROMOSOMES

- Human Cell

## DNA/CHROMOSOMES

## 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**

## GENES to PROTEINS

## 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.

## 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

## Base Substitutions change the DNA sequence

## DNA sequence changes can change proteins

## Chromosomal rearrangements

- Loosing genes                 Moving genes

## Tumor cell karyotype

## Two general causes of mutations

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

## DNA polymerases copy the DNA

## DNA polymerases copy the DNA

## DNA polymerases make mistakes

- Sometimes polymerases put in the wrong nucleotide

- Mutation?

**Base substitution**

## DNA polymerases make mistakes

- Damaged bases are hard to read, causing polymerase errors

- Mutation?

**Base substitution**

## DNA polymerases make mistakes

- Sometimes the polymerase complex collapses

- Mutation?

**Chromosomal rearrangement**

## Sometimes the helix just breaks

- Mutation?

**Chromosomal rearrangements**

## 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

## 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.

## Mismatch Repair

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

- Mutations prevented?

**Base substitutions**

## Excision Repair

- Removes damaged bases and replaces them before a DNA polymerase stumbles through them.

- Mutations prevented?

**Base substitutions & Chromosomal rearrangement**

## Break Repair

- Repair mechanisms used to attach broken ends of DNA to restore chromosome integrity.

- Mutations prevented?

**Chromosomal rearrangements**

## 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**

## 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.

## Oncogenes support cell growth

*Onco-* = tumor (Greek)
- Encode proteins that control cell growth
- (proto-oncogenes)

## Cells require a balance of tumor suppressor and oncogene activity

- Tumor Suppressors

- Oncogenes

## Too many tumor suppressor activities can lead to cell growth arrest or death

- Tumor Suppressors

- Oncogenes

- Slow down
- Obey
- Stay put
- Repair carefully

## Too much oncogene activity can lead to increased/uncontrolled cell division 

- Tumor Suppressors

- Oncogenes

- Grow!
- Grow!
- Grow!
- Grow!

## 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

## 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

## 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

## How DNA repair prevents cancer

- DNA damage is continuous and stochastic

- Most damage is repaired

## Audience tumor drill #1Spontaneous tumors

- You are the cells!
- Will any of you become tumors?

## Ultraviolet light causes cancer

- Cells from which tissues become tumors?

## Audience tumor drill #2Sunbathing-induced tumors

- You are the cells!
- Will any of you become tumors?

## Smoking causes cancer

- Cells from which tissues become tumors?

## Audience tumor drill #3Smoking-induced tumors

- You are the cells!
- Will any of you become tumors?

## 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**

## Cancer rates

- Incidence

- Mortality

## What can you do to prevent cancer?

- Don’t smoke or use tobacco products
- Wear sunscreen, and avoid UV exposure
- Good diet (Fruits & Veggies)
- Regular exercise
- Medical exams/self exams

## Cancer information Websites

- American Cancer Society:
- http://www.cancer.org
- National Cancer Institute:
- http://www.cancer.gov/
- Surveillance Epidemiology and End Results (Statistics):
- http://seer.cancer.gov/
- The Skin Cancer Foundation:
- http://www.skincancer.org/
- Lung Cancer Foundation:
- http://www.lungcancer.org/
- Harvard Center for Cancer Prevention:
- http://www.hsph.harvard.edu/cancer/

## 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!

## How to become a Cancer Researcher

- College (bachelor’s degree)
- _Subjects (majors/minors):_
- Biology, Chemistry, Physics, Math, Computer sciences

- _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)

- _Research experience_
- Summer student opportunities, hospital /lab volunteer work

## John

**John**

**Toxic**
**Fumes**

**Salustra**

**Cells**