However most mutations are recessive and require

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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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This document was uploaded on 02/25/2014.

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