DNA Damage and Repair Mechanisms

Environmental and Metabolic Agents

Environmental agents damaging cells:
- UV radiation
- Chemical exposure (air pollution, cigarette smoke)
Metabolic byproducts such as free radicals also cause damage
Damage leads to changes in DNA

Estimated 1 million DNA changes per cell per day
DNA repair is a complex, regulated sequence
Features three main molecular machines:
1. Machine 1: Searches for broken DNA and initiates repair
2. Machine 2: Assembles a chain linking to Machine 3
3. Machine 3: finalizes the repair complex

Final molecule in repair complex
Formed from two halves which bind together
Recruits further complexes for DNA repair
Inherited Variants in BRCA1:
- Can alter protein function
- Interrupts DNA repair
- Leads to accumulation of DNA damage
Increased risk for cancers:
- Breast and ovarian cancer (50-80% and 30-50% lifetime risk, respectively)
- Pancreatic and prostate cancer

Women's choices with BRCA1 alterations:
- Constant surveillance
- Preventive surgeries (ovaries, mastectomy)
- Medication (tamoxifen)

Leading cancer research, education, and treatment center in Australia
Largest cancer research site in Australia
Focus on biological & biomedical discoveries and applications
Offering state-of-the-art diagnostic and treatment services
Parkville Familial Cancer Center:
- Cancer risk assessment
- Genetic testing and counseling
- Medical advice and management
- Psychological support
Involved in cancer prevention strategies:
- Ban on smoking
- Ban on commercial tanning beds