BCHM 4116 1st Edition Lecture 21Outline of Last Lecture I. DNA Repair Outline of Current Lecture I. DNA Repair Current Lecture1. DNA Repaira. Human genome has 150 genes associated w/ DNA repair b. DNA repair system includes:i. Direct reversal damage repair1. Chem. Rxn that reverse damage, returning DNA to proper stateii. Single-strand damage repair1. Relies on complementary strand to guide repair 2. Mismatch repair (MMR) a. Mismatched during replicationb. Scans, excises mismatched region, replacesc. KEY to tell which strand is newly synthesized and thus contains mismatch is via METHYLATIONi. 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 strand3. Base excisiona. 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 sitec. AP ENDONUCLEASEi. Cleaves backbone & removes deoxyribose-P d. DNA Poli. Repairs gape. DNA ligasei. 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 gapd. 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 helix2. 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 recombinationa. 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 light1. UV irradiation causes covalent bonding of adjacent thymine residues in DNA,creating cyclobutyl ring – leaves DNA DISTORTED & therefore no longer a proper template2. PHOTOLYASE: a flavin & protein-dependent enezyme binds at dimer & uses energy of visible light to break cyclobutly ring
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