The Mutability and Repair of DNA
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The Mutability and Repair of DNA. REPLICATION ERRRORS AND THEIR REPAIR. The nature of mutations. Transitions. Transversions. Some replication errors escape proofreading. Mismatch repair removes errors that escape proofreading. Structure of MutS and DNA

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The Mutability and Repair of DNA

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The Mutability and Repair of DNA

REPLICATION ERRRORS AND THEIR REPAIR

The nature of mutations

Transitions

Transversions


Some replication errors escape proofreading


Mismatch repair removes errors that escape proofreading


Structure of MutS and DNA

(MutS recognizing mismatches from the distortion they cause)


Dam methylation in E. coli replication fork


Directionality in mismatch repair


DNA DAMAGE

DNA undergoes damage spontaneously from hydrolysis and deamination


DNA is damaged by alkylation, oxidation, and radiation


Thymine dimer caused by UV light


Base analogs and intercalating agents that cause mutations in DNA


Ames test for carcinogens


Bruce N. Ames

Professor of the Graduate School Division of Biochemistry and Molecular Biology, UC Berkeley


REPAIR OF DNA DAMAGE


Direct reversal of DNA damage


Direct removal of the methyl group from O6 -methylguanine


Base excision repair enzymes remove damaged bases by a base-flipping mechanism


Structure of DNA-glycosylase complex


How is an altered base detected within the context of the double-helix?

The recognition of an unusual nucleotide in DNA by base-flipping of glycosylase


Oxo-G:A repair by a fail-safe glycosylase


Nucleotide excision repair enzymes cleave damaged DNA on either side of the lesion


Transcription-coupled DNA repair


Recombination repair DNA breaks by retrieving sequence information from undamaged DNA

Double-Strand Breaks are Efficiently Repaired


DSBs in DNA are also repaired by direct joining of broken ends


Translesion DNA synthesis enables replication to proceed across DNA damage


Structures of a translesion polymerase and a typical polymerase


Mutations are linked to cancer


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