Examples enol tautomer of t pairs with g imino

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Examples: Enol tautomer of T pairs with G Imino tautomer of A pairs with C Enol tautomer of G pairs with T Imino tautomer of C pairs with A.
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Lecture 10: DNA damage, mutation, repair 8 • If the template base or the incoming base is in the wrong tautomeric form, an incorrect base may be inserted and not immediately corrected. • This leads to a mismatched base pair at a frequency of about 10 -6 . Usually the 3'->5' exonuclease activity catches these, but they can escape at a frequency of about 10 -4 . The total frequency of replication errors is thus near 10 -10 . • If not corrected before the next replication cycle, the two daughter duplexes will have different base pairs at the position of the original mispair. • Intercalating dyes such as ethidium bromide or acridine can cause insertions and deletions due to binding of the dyes to primer template complexes. Replication errors
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Lecture 10: DNA damage, mutation, repair 9 Chemical Damage • Spontaneous hydrolysis of the glycosidic bond. Produces an abasic site (backbone stays intact). • Deamination of cytosines: Spontaneous. Causes Transitions C to T and G to A.
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Lecture 10: DNA damage, mutation, repair 10 Chemical Damage cont’d • Alkylation of bases and phosphates. Chemicals: Dimethylsulfoxide, Ethanemethylsulfonate, N-methyl- N-nitrosourea (nitrosamines), nitrosoguanidine. Example: O 6 - methylguanosine can pair with T, causes G to A transitions. Free radicals, (hydroxyl radical, superoxide ion, often from respiratory reactions) Example: 8- oxoguanosine. Can pair with A. Causes G to T and C to A transversions.
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Lecture 10: DNA damage, mutation, repair 11 Thymine glycols, produced by oxidation of the 5-6 double bond, ring no longer planar and G can be inserted.
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Lecture 10: DNA damage, mutation, repair 12 Photochemical damage (ultraviolet) • Pyrimidine dimers, Cyclobutane ring forms between adjacent pyrimidines on the same strand. Creates a backbone distortion and blocks replication. • Crosslinking to proteins, less common but occurs. • Interstrand crosslinks (esp in conjunction with chemicals, example: psoralens intercalate and crosslink to pyrimidines on opposite strands).
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Lecture 10: DNA damage, mutation, repair 13 • Ionizing radiation -> double strand breaks • Physicochemical damage (Shearing) DNA is a long molecule that is subject to shear forces: double strand breaks. • Errors in repair of damaged DNA. Severe damage to DNA from chemicals or UV that overwhelms normal repair systems leads to induction of the SOS system. This results in error prone repair by translesion DNA polymerases. • Errors in recombination. Homologous recombination between similar but not identical sequences. Nonhomologous recombination. • Insertion of mobile genetic elements (IS sequences, Transposons) A number of different kinds of transposons can insert themselves into DNA. Other kinds of damage
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Lecture 10: DNA damage, mutation, repair 14 Mutations in Polymerase subunits reveal polymerase contributions to reducing errors • Mutations in the gene encoding the alpha subunit of pol III are known which cause higher or lower rates of misincorporation.
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