Lecture 4

Lecture 4 - Lecture #4 DNA Repair MBOC (old) Page 267-285...

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Lecture #4 DNA Repair MBOC (old) Page 267-285 MBOC (new) Page 295-311
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Concepts • What can induce DNA Damage • Describe repair mechanisms for the following errrors – Single nucleotide errors – Small regions of mismatch – Double strand breaks • What is homologous recombination
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DNA Replication has Proofreading mechanisms • DNA polymerase III has two proofreading mechanisms – Correct nucleotide has high affinity for the moving polymerase – Conformational change in DNA polymerase III is required after nucleotide binding but before covalent addition - check DNA strand • Exonuclease proof-reading activity – Only adds to the 3’ -OH of a primer strand – Mismatched nucleotides do not make a correct base- pair, thus disrupting the primer
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DNA editing mode of DNA Polymerase III
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DNA editing mode of DNA pol III
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DNA polymerase III
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What happens in catastrophic cases of DNA damage? • If a cells DNA is heavily damaged the classic DNA repair pathways can not operate • Replicative DNA polymerase stalls when it encounters DNA damage in catastrophic emergencies – less accurate back-up DNA polymerases are used – Human cells have >10 such polymerases – Some recognize specific types of DNA damage – Others make “good guesses” • Lack exonuclease proof reading activity
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Why is DNA repair so important?
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What creates and/or propagates DNA damage? • UV radiation (sun burn) • Irradiation (X-ray machines) • Chemicals (ENU) • Errors in DNA repair mechanisms
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Syndromes in Humans caused by defects in DNA repair machinery
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Repairing a single nucleotide error
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Some types of DNA damage occurs spontaneously in cells • DNA in human cells lose ~ 5,000 purine bases (A, G) every day – N-Glycosyl linkage to deoxyribose hydrolyses • DEPURINATION – Removal of amine groups from bases • DEAMINATION – Every 100 bases per cell every day
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Example of Depurination Result is absent base but an intact sugar phosphate backbone
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Example of Deamination This hydrolysis occurs ~100 bases per day
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Special circumstance of methylated C residues ~ 3% of C residues are methylated in vertebrates Deamination of C residues results in generation of ‘T”
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Pyrimidine dimers • Usually occurs in cells exposed to UV irradiation • These form between two neighboring pyrimidines • The most common are thymidine dimers
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Method by which chemical modifications produce mutations
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This note was uploaded on 03/30/2009 for the course MCDB 144 taught by Professor Dr.clarkanddr.lowry during the Spring '09 term at UCLA.

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Lecture 4 - Lecture #4 DNA Repair MBOC (old) Page 267-285...

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