1 / 18

Mutations, Mutagenesis, and Repair

Mutations, Mutagenesis, and Repair. Chapter 10 . The Problem. DNA extremely long, fragile Subject to both physical and chemical damage Consequences could be lethal for organism or offspring. }. Frameshift mutations. Mutation. A heritable change in the base sequence of DNA

wright
Download Presentation

Mutations, Mutagenesis, and Repair

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Mutations, Mutagenesis, and Repair Chapter 10

  2. The Problem • DNA extremely long, fragile • Subject to both physical and chemical damage • Consequences could be lethal for organism or offspring

  3. } Frameshift mutations Mutation • A heritable change in the base sequence of DNA • Point mutation- change in a single base position • Additions • Deletions • Substitutions • Transitions • Transversions • Multiple mutations

  4. Consequences of Mutation • Silent Mutation---base change, no amino acid change • Neutral Mutation--- Base change resulting in aa change that does not affect protein function • EX. Apartic acid (D) Glutamic acid (E) • Missense mutation---altered codon, new aa with different chemical properties. Function affected. • Nonsense mutation---base pair substitution results in a stop codon (and shorter polypeptide) • Frameshift mutations—additions or deletions. Peptide may be longer or shorter. • Sense mutation?

  5. Other Terms • Conditional Mutation—wild type function except under certain (permissive) conditions • Ex. Temperature sensitive mutants show mutant phenotype only at certain temperatures • Leaky mutations— a missense amino acid change that reduces but doesn’t eliminate protein function

  6. Mutagenesis • The process of mutation • Mutagen—anything that promotes ort causes mutations • Chemical • Physical

  7. Mutation-Causes • Incorrect base pairing due to tautomeric shifts • Removal of nitrogenous bases • Alteration of nitrogenous bases • Addition or deletion of nucleotides • Single strand breaks • Double strand breaks • Crosslinking—covalent linkage between bases

  8. Spontaneous Mutations • Arise without mutagenic agents. DNA pol has proofreading function, can remove mismatched base • Even if DNA pol misses a mismatch other systems can recognize and repair it. • Recognition? • Hemimethylation-allows enzymes to distinguish between parent and daughter strands.

  9. } Altered H-bonding Spontaneous Mutations • Tautomeric shifts during replication. • Depurination—if a purine base is lost from C-1 of deoxyribose, will get apurinic site. • Odds of misincorporation on the daughter strand=75% • Enzymes specific for this type of mutation have evolved • Deamination. • CU • AHypoxanthine

  10. Tautomers and Mutation Normal base pairing Rare imino forms of adenine and cytosine Rare enol forms of thymine and guanine Back

  11. Deamination of C and A • CU • 3 H-bonds w/G2 H-bonds w/A • AHypo-xanthine • 2 H-bonds w/G3 H-bonds w/C

  12. Removing and Replacing Uracil • Uracil automatically removed from DNA by uracil N-glycosylase • AP Endonuclease cuts 5’ to apurinic site • Sugar phosphate removed by phosphodiesterase • DNA pol I adds correct base • Ligase seals • Base Excision Repair (BER)

  13. G G P P P P P P P P P P P P P P P P T C G T U C G A G C A G G C A G C A C P P P P P P P P P P P P P P Base Excision Repair (BER) Uracil DNA glycosylase AP endonuclease G DNA polymerase I G T C C G DNA ligase T G

  14. 5 Methyl Cytosine Deamination • Easily recognized and corrected • What about 5-methyl cytosine? • Is there a problem? • Always remove T from a GT pair ?

  15. Deamination of Cytosine and 5-methylcytosine -------------------------------------------------------------------------------

  16. Induced Mutations • Caused by exposure to a mutagen • Causes • Exposure to base analogs • Chemical mutagens • Intercalating agents • Uv- radiation • Transposable elements • Mutator genes

  17. Exposure to Bases Analogs • Base analogs—substances that are similar to and can substitute for standard bases • Examples—AZT, 5-bromouracil (5-BU) and 2-aminopurine (2-AP)

  18. 5 Bromouracil THE PROCESS A·T • The Problem: 5 bromouracil assumes the enol form at a much higher frequency than T • if it replaces T, will probably get a mutation due to tautomerization during replication • Result: A·T G·C Replication in presence of BrU A·BrU Tautomeric shift A·BrU* Replication A·T + G·BrU* Replication A·T + A·T + G·BrU* + GC

More Related