GDCB 511-4-20-09

GDCB 511-4-20-09 - GDCB 511: 20 April 2009 DNA Damage and...

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GDCB 511: 20 April 2009 DNA Damage and Repair Damage causes Alkylation Ultraviolet radiation Gamma and X-rays Repair Direct undo Excision repair Double-strand break repair in eukaryotes Mismatch repair Failure of mismatch repair in humans Coping with DNA damage without repairing it
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EMS donates an ethyl group to the O 6 oxygen of guanine. O 6 -ethylguanine base-pairs with thymine instead of cytosine. After one round of DNA replication, an A-T base pair will have replaced a G-C pair. Repair of mutations caused by mutagens: alkylation of guanine by ethylmethane sulfonate (EMS)
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O6-methylguanine methyl transferase accepts the methyl group from the guanine on DNA, thus inactivating the enzyme
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Pyrimidine dimer: UV light causes covalent linkage of adjacent thymines to form a cyclobutane ring
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Model for photoreactivation repair of thymine dimer by DNA photolyase ( E. coli ). UV light causes pyrimidine dimer to form. Photolyase binds to this region. The enzyme absorbs near UV to visible light and breaks the dimer.
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Base Excision Repair (BER) in E. coli for repair of minor base damage a) DNA glycosylase removes the damaged base (red), leaving an apurinic or apyrimidic (AP) site b) AP endonuclease cuts the DNA on the 5’ side of the AP site c) DNA phosphodiesterase removes the AP-deoxyribose phosphate d) DNA polymerase I fills in the gap and continues repair synthesis for a few nucleotides downstream, degrading DNA and simultaneously repairing it e) DNA ligase seals the nick left by DNA polymerase
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The human BER pathway a)Spontaneous cytosine deamination converts C to U b) Glycosylase removes U c) APE1 cleaves on 5’ side of AP site d) DNA pol β fills in the gap e) DNA ligase seals the nick f) Occasionally, DNA pol β makes a mistake g) APE1 uses its 3’- exonuclease to remove the mispaired base, leaving a gap h) DNA pol β inserts the correct base e) DNA ligase seals the nick What’s wrong in this figure?
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GDCB 511-4-20-09 - GDCB 511: 20 April 2009 DNA Damage and...

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