13.14.repair - DNA damage and repair summary 1 Defects in r epair cause disease 2 Common types of DNA damage 3 DNA r epair pathways Direct

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Unformatted text preview: DNA damage and repair summary 1. Defects in r epair cause disease 2. Common types of DNA damage 3. DNA r epair pathways Direct enzymatic repair Base excision repair Nucleotide excision repair Mismatch repair Double-strand break repair Non-homologous end joining Homologous recombination DNA repair defects cause disease Common types of DNA damage -- 1 1. Depur ination: A, G 2. Deamination: C --> U, A --> H ypoxanthine Common types of DNA damage -- 2 Pyr imidine dimer s (UV induced). Repair pathways Common types of DNA damage -- 3 Two car cinogens that mutate (the P53 gene) by base alkylation + M ismatches (mistakes in DNA synthesis) I nter str and cr oss-links, Double-str and DNA br eaks 4 6 Diverse DNA repair systems • Augment DNA polymer ase pr oofr eading • M ostly char acter ized in bacter ia • Gener al mechanisms shar ed in eukar yotes 1. Dir ect r epair , e.g. pyr imidine dimer s 2. Base excision r epair 3. Nucleotide excision r epair 4. M ismatch excision r epair 5. Double-str and br eak r epair and r ecombination Base excision repair Base excision r epair pathway (BER). (a) A DNA glycosylase r ecognizes a damaged base and cleaves between the base and deoxyr ibose in the backbone. (b) An AP endonuclease cleaves the phosphodiester backbone near the AP site. (c) DNA polymer ase I initiates r epair synthesis fr om the fr ee 3’ OH at the nick, r emoving a por tion of the damaged str and (with its 5’ → 3’ exonuclease activity) and r eplacing it with undamaged DNA. (d) The nick r emaining after DNA polymer ase I has dissociated is sealed by DNA ligase. AP= apurinic or apyrimidinic (a=without) Damaged base A DNA glycosylase initiates base excision repair Examples of bases cleaved by DNA glycosylases: Ur acil (deamination of C) 8-oxoG pair ed with C (oxidation of G) Adenine acr oss fr om 8-oxoG (misincor por ation) Thymine acr oss fr om G (5-meC deamination) Alkyl-adenine (3-meA, 7-meG, hypoxanthine) Damaged base H uman alkyl-adenine DNA glycosylase DNA bent & modified base flipped out of duplex -- “Non-Watson-Cr ick” str uctur e Diverse DNA repair systems • Augment DNA polymer ase pr oofr eading...
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This note was uploaded on 03/08/2010 for the course MCB 110 taught by Professor Alber,zhou,nogales during the Fall '07 term at University of California, Berkeley.

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13.14.repair - DNA damage and repair summary 1 Defects in r epair cause disease 2 Common types of DNA damage 3 DNA r epair pathways Direct

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