BCHM 4116 1st Edition Lecture 21 Outline of Last Lecture I DNA Repair Outline of Current Lecture I DNA Repair Current Lecture 1 DNA Repair a Human genome has 150 genes associated w DNA repair b DNA repair system includes i Direct reversal damage repair 1 Chem Rxn that reverse damage returning DNA to proper state ii Single strand damage repair 1 Relies on complementary strand to guide repair 2 Mismatch repair MMR a Mismatched during replication b Scans excises mismatched region replaces c KEY to tell which strand is newly synthesized and thus contains mismatch is via METHYLATION i Newly synthesized strands are not yet methylated whereas parent strand is d Endonuclease cuts new unmethylated strand exonuclease removes mismatched base DNA pol III holoenzyme fills gap w correct bases ligase reseals strand 3 Base excision a For single bases that have been damaged via oxidation or other chemical modification b DNA GLYCOSYLASE removes damaged base i Cleaves N glycosidic bond creates AP site c AP ENDONUCLEASE i Cleaves backbone removes deoxyribose P d DNA Pol i Repairs gap e DNA ligase i Reseals 4 Nucleotide excision a Repairs larger regions of damaged DNA than base b Cuts sugar phosphate backbone of DNA These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute c DNA Pol fills in gap d DNA ligase reseals Cont iii Double stranded damage repair DSB 1 Threat to genome stability b c lost sequence cannot be recovered from same DNA double helix 2 Simplest way to repair is to rejoin broken strands through nonhomo DNA end joining NHEJ 3 Problem w NHEJ is to keep ends near each other so can be linked later 4 DSP repair through homologous DNA recombination a dsDNA with damage pairs with sister chromatid and then cuts at damage and copies correct sequence from sister and may or may not go through recombination with sister iv Translesion DNA synthesis 1 Tolerance mechanism than a repair mechanism b c it allows replication w out necessarily repairing the damage v UV light 1 UV irradiation causes covalent bonding of adjacent thymine residues in DNA creating cyclobutyl ring leaves DNA DISTORTED therefore no longer a proper template 2 PHOTOLYASE a flavin protein dependent enezyme binds at dimer uses energy of visible light to break cyclobutly ring
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