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DNA Repair

dna repair of gene mutations

DNA repair - most mechanisms require two nuc strands of DNA - replace whole nucs & temp strand need to specify base sequence - Redundent: damage fixed in more than one way
Proofreading - corrects 99% of errors in replication - wrong base= incorrect positioning of 3'-OH group at active site of DNA plymerase to bond with next nuc= stalls polymerization rxn, 3'5' exonuclease activity removes Wbase
Mismatch repair Bacteria: mutS scans DNA for lesion by bending and testing minor groove Eukaryotes/Humans: MSH2 is like MutS. Mutation in one allele leads to HNPCC cancer - corrects replic errs which produce a deformity in the 2ndary structure of DNA - deformity is recoged by enzymes, excise Wpaired nuc.& use orig nuc strand as template to replace Wnucleotid - must recognize old strand from new to know whatbase to remove
How mismatch IDs old strand from new strand of DNA - E. coli, (−CH3) added to particular nuc sequence only after replication, immedly after DNA synth, only the old strand is methylated. - recognized & MR takes place on the unmethylated nucl strand
Direct repair - changes back altered nucleotide, not replace (bact& euk) - photoreactivation of UV-induced pyrimidine dimers: photolyase enzyme uses E from light to break the cov bonds b/w pyrimidines in a dimer via methyltransferase - correction of O6-methylguanine
Base-excision repair - repairs Abnormal bases, modified bases, and pyrid dimers - glycosylase enzymes recognize and excise specific types of modified bases. - entire nuc is then removed & section of the polynucleotide strand is replaced
Nucleotide-excision repair (acts anytime in cell cycle) - bulky DNA lesions that distorts the double helix, including abnormal bases, modified bases, and pyrimidine dimers - the most impo, found in cells of all organisms - The2 DNA strands r separated,section of the DNA containing the distortion removed, DNA
COMPARE ALL REPAIR MECHANISMS - most require presence of two strands, damage is removed, replaced (except in direct repair) - all: detection, excision DNA-repair endonucleases, polymerization by DNA polymerase add new nucs to 3'-OH, Ligation to seal
DIFFERENCES IN REPAIR MECHANISMS -In base-excision and MR, singlenick imade in the sugar–phosphate backbone on one side of the damage; IN nucl-excision repair, nicks on both sides - In base-excision repair, DNA poly displaces old nucs as it adds new nucs to the 3′ end of the nick; IN MR
Double-Strand Breaks Repair - break in DNA helix caused by ionizing radiation, oxidtive free radicals, and other agents - determental: stall DNA replication, lead to chrome rearrangment(deletion, dup, inversion, translocations) 2 Repair mechanisms: homo recomb& nonhomo end joining
Homologous recombination - repair using id'ical or close genetic info contained inanother DNA molecule, usually a sister chromatid - begins with the removal of some nucleotides at the broken ends, followed by strand invasion, displacement, and repli key enzymes: BRCA1 and BRCA2
Nonhomologous end joining - repairs double-strand breaks w/out a homologous template - used when the cell is in G1 & sister chromatid not available -uses proteins that recognize the broken ends of DNA, bind to the ends, and then joins them together -more error prone Insrt/del
Translesion DNA Polymerases - When distortions of the template are encountered, specialized translesion DNA polymerases take over replication and bypass the lesion -allow replication to proceed but introduce more error/mutations
polymerase η (eta) - a translesion DNA polymerase, bypasses pyrimidine dimers in eukaryotes -inserts AA opposite a pyrimidine dimer since about two-thirds of pyrimidine dimers are thymine dimers -However, Results in a C · G→A · T transversion- new mutation introduced
Photoactivated repair -direct repair of thymine dimer- photolyase enzyme -uses blue light to provide energy -not present in placental mammals
SOS repair bacteria -error prone but last chance -finds replacement templates from other copies of DNA in cell instead of other strand -uses translesional DNA polymerases to replicate through altered stretches of DNA
MMR Adenine methylation at GTAC Sequence of old strand MMR-complex Exonucleases - 1nick DNA Polymerase DNA Ligase
B-E R DNA glycosylases - remove base Apurinic/Apyrimidic Site Corresponding endonuclease - 1 Nick exonuc activity DNA Polymerase DNA Ligase
N-E R Complex of enzymes additional enzymes SSBinding Proteins an enzyme - 2 nicks helicase enzyme DNA Polymerase DNA Ligase
Created by: Yourdanos