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 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