Depurination

• Release of adenine or guanine bases

Deamination

• Often converts cytosine to uracil

Pyrimidine Dimers

• Linkage of adjacent pyrimidine bases

Summary Of DNA Damage

• hydrolysis (including depurinations and deaminations) • oxidation• methylation

Replication Of Deaminated Cytosine

Replication Of Depurinated Nucleotide

Base Excision Repair• Remove damaged base using

DNA glycosylase• Cut phosphodiester backbone• Fill in gap

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

Nucleotide Excision Repair

Multienzyme complex• Recognizes bulky lesion• Cuts phosphodiester backbone

Repair of Double Strand Breaks

• NHEJ: Ligation of broken ends with loss of sequence• HR: Undamaged sister chromatid as template

Diseases Of DNA Repair

Xeroderma pigmentosum

Nucleotide excision repair

UV sensitivity, skin cancer

BRCA-1, BRCA-2

Repair by homologous recombination

Breast and ovarian cancer

Hereditary nonpolyposiscolon cancer

Mismatch repair

Colon cancer

Disease Defective Process Effect