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Unformatted text preview: he acute effects were suffered
increased incidence of many types of cancer • These excess cancers are still being detected in this population.
• Why cancer?
• Animal studies have detected genetic effects from sublethal doses
of radiation. Radiation Exposure in Humans:
The Heavy • No such effects have been detected in offspring of Japanese
survivors. • However, most mutations are recessive and require several
generations to detect - why?
2 copies needed to show phenotype A number of pathways repair
changes in DNA
• More than 999/1000 DNA lesions are repaired before being passed on.
• General characteristics of DNA repair
• Most DNA repair mechanisms require two strands of DNA
• A template strand is needed to specify the correct nucleotide
sequence. • Many types of DNA damage can be repaired by more than one
pathway. • Why? A number of pathways repair
changes in DNA • Four mechanisms of DNA repair:
• Mismatch repair
• Direct repair
• Base-excision repair
• Nucleotide-excision repair Mismatch repair corrects errors
missed by proofreading • Mismatched bases are incorporated into a new DNA strand
during synthesis at a frequency of about 1 in 10,000 or 100,000. • However, most errors are corrected and never become permanent
mutations. • Proofreading by the DNA polymerase.
• Mismatch repair. Mismatch repair corrects errors
missed by proofreading • Errors distort the 3D structure of DNA
• Mismatch enzymes detect these distortions
• Also detects small unpaired loops in DNA
• e.g. those caused by strand slippage in replication.
• If trinucleotide repeats form secondary structures.
they may escape detection. Mismatch repair corrects errors
missed by proofreading
• Mismatch-repair enzymes cut out the distorted part of the
new strand • Fill in using the original strand as a template.
• Differentiate between new and old strands
• In E. coli, after synthesis, adenine nucleotides in the
sequence GATC are methylated. • Immediately after synthesis, only the old strand is
methylated. Mismatch repair
• Mismatch repair in
eukaryotic cells is
similar to that in E. coli
• It is not known how old
and new strands are
recognized. For Wednesday: Finish Chapter 18: Mutation and DNA Repair
Begin Chapter 19: Recombinant DNA technology...
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