1. Depurination
Release of adenine or guanine bases

2. Deamination
Often converts cytosine to uracil

3. Pyrimidine Dimers
Linkage of adjacent pyrimidine bases

4. Summary Of DNA Damage
hydrolysis (including depurinations and deaminations)
oxidation
methylation

5. Replication Of Deaminated Cytosine

6. Replication Of Depurinated Nucleotide

7. Base Excision Repair Remove damaged base using DNA glycosylase
Cut phosphodiester backbone
Fill in gap

8. Damage Detection in Deaminated DNA Bases
Deamination leads to unnatural base, removed by DNA glycosylase
Exception: Deamination of methylated C at CG dinucleotide generates T that is inefficiently removed
Methylated C common site for mutation

9. Nucleotide Excision Repair
Multienzyme complex
Recognizes bulky lesion
Cuts phosphodiester backbone

10. Repair of Double Strand Breaks
NHEJ: Ligation of broken ends with loss of sequence
HR: Undamaged sister chromatid as template

11. Diseases Of DNA Repair Disease Defective Process Effect
Xeroderma pigmentosum
Nucleotide excision repair
UV sensitivity, skin cancer
BRCA-1, BRCA-2
Repair by homologous recombination
Breast and ovarian cancer
Hereditary nonpolyposis
colon cancer
Mismatch repair
Colon cancer