08-16 DNA Repair (RB) - DNA REPAIR Ruth Borghaei, Ph.D....

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Unformatted text preview: DNA REPAIR Ruth Borghaei, Ph.D. Polymerase error is a minor source of DNA damage Types of DNA damage Depurination Spontaneous loss adenine or guanine nitrogenous base ~5000/cell/day Deamination Common, spontaneous loss of NH 2 Results in unusual bases not usually found in DNA ~100/cell/day Oxidative damage to nucleotides >80 different types of base damage due to reactive oxygen species 8-hydroxyguanine, (8-oxoG) base-pairs with A instead of C Natural DNA Base Unnatural base after deamination Adenine Hypoxanthine Guanine Xanthine Cytosine Uracil Thymine No deamination Methyl C Thymine Unrepaired damage leads to mutation Overview DNA repair Less than 1 in 1000 accidental base changes results in permanent change = mutation Double stranded structure of DNA makes it ideally suited for repair Over 100 different proteins are known to be involved in the 5 major pathways of repair: Mismatch repair (MMR) Base excision repair (BER) Nucleotide excision repair (NER) Homologous recombination (HR) Non-homologous end-joining (NHEJ) Strand-selected DNA mismatch repair (MMR) Reduces error rate of DNA replication by additional 10 2 Repairs polymerase error and small insertions or deletions Important for stability of microsatellites Mutation of MMR enzymes is associated with inherited colorectal Mismatch Repair (MMR) Proteins scan DNA for small structural distortions Strand selection likely based on more nicks in newly synthesized strand Area between mismatch and nick is excised DNA pol fills gap Ligase seals nick Excision repair Most common type of repair in human cells Subtypes Base excision repair (BER) Nucleotide excision repair (NER) Transcription-coupled repair (TCR) Global genome repair (GGR) Basic steps of excision repair Recognize damage Remove damage by excising part of the damaged strand Fill in gap, using other strand as template Ligate to seal nicks DNA glycosylases in BER Family of enzymes that recognize specific types of damaged nitrogenous bases Deaminated Cs, As Alkylated or oxidized bases Bases with opened rings Bases with reduced double bonds Catalyze removal of the damaged nitrogenous base by hydrolysis of the N- glycosidic bond Base excision repair...
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This note was uploaded on 05/31/2011 for the course BIOMED 1 taught by Professor Dr.borghei during the Fall '10 term at Philadelphia College of Osteopathic Medicine.

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08-16 DNA Repair (RB) - DNA REPAIR Ruth Borghaei, Ph.D....

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