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Mutations, DNA replication, Cancer

Mutations, DNA replication, Cancer. A single mutation caused this. Cystic fibrosis (accumulation of mucus in lungs) is due to a ___. A. Faulty lysosome B. Faulty cell membrane C. Faulty cytoskeleton D. All of the above. Genetic information flows in cell from DNA  RNA  protein.

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Mutations, DNA replication, Cancer

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  1. Mutations, DNA replication, Cancer A single mutation caused this

  2. Cystic fibrosis (accumulation of mucus in lungs) is due to a ___ A. Faulty lysosome B. Faulty cell membrane C. Faulty cytoskeleton D. All of the above

  3. Genetic information flows in cell from DNA  RNA  protein. Review of Protein Synthesis Each gene on DNA codes for production of a specific polypeptide/protein.

  4. Mutations

  5. Cancer • Breast Cancer • Two human genes, called BRCA1 and BRCA2 • >200 different changes in the DNA sequences http://learn.genetics.utah.edu/content/begin/dna/neurofibromin/

  6. Sickle cell Anemia

  7. Mutation: A change in the nucleotide sequence of DNA. http://www.cancer.gov/cancertopics/UnderstandingCancer/genetesting

  8. Mutation: A change in the nucleotide sequence of DNA. Causes of mutations 1. Radiation 2. Chemical 3. Spontaneous

  9. How does smoking/UV rays damage DNA? 1. Modify nucleotide bases

  10. Phosphate backbone is broken

  11. 2. Mistakes during DNA duplication (spontaneous mutation)

  12. Nobel Prize in Chemistry 2015 Tomas Lindahl, Paul L. Modrich and Aziz Sancar were awarded the Nobel Prize in Chemistry for having mapped and explained how the cell repairs its DNA and safeguards its genetic information.

  13. Point mutations 1.Base insertion 2. Base deletion 3. Base substitution • Chromosomal aberrations • Gene deletion • Gene relocation • Gene duplication

  14. Types of point mutations • Base substitution Silent mutation: No change in amino acid sequence and so no new protein is formed Sometimes silent mutations

  15. Base insertion • Base deletion

  16. Frame shift Reading frame shifts when there is base insertion or base deletions

  17. Are mutations Harmful or Beneficial?? Depends on the particular gene mutation

  18. Examples of favorable mutations Resistance to Atherosclerosis Increased bone density Mutations in a gene protects people from diabetes. They produce more insulin Sickle cell resistance to malaria HIV resistance Orange color mutation leads to more nutritious cauliflower Red heads more resistant to anesthetics!

  19. Genetic mutation Basis of species diversity

  20. Hereditary Mutation: either present in egg, sperm or the zygote http://www.cancer.gov/cancertopics/UnderstandingCancer/genetesting

  21. http://www.cancer.gov/cancertopics/UnderstandingCancer/genetestinghttp://www.cancer.gov/cancertopics/UnderstandingCancer/genetesting

  22. Natural protection against mutation • DNA proofreading • DNA repair • checking RNAs and proteins 4. Redundant Genetic code

  23. Certain mutations are called “silent” because ___ • A different protein is formed • No new protein is formed • A different amino acid sequence is formed • No new amino acid sequence is formed E. Both B and D

  24. What is the difference between normal and sickle cell hemoglobin at the primary level? • The linear sequence of amino acids are different • The shape of the protein is different • The coils and pleats of the protein are different • All of the above are different

  25. Mutation A Mutation B • Which mutation is germ-line (hereditary) mutation? • Mutation A • Mutation B

  26. DNA Replication • Relies on specific pairing of matching bases • One strand of DNA carries all the information needed to construct its complementary strand.

  27. DNA Replication also known as DNA duplication: Just before cells divide, the DNA molecule unwinds and each half of the unwound DNA molecule serves as the template for the new strand of DNA to be constructed by the enzyme DNA polymerase. AT the end of DNA replication there are two DNA molecules---each identical to the original DNA molecule.

  28. duplicated Unduplicated

  29. DNA replication(DNA duplication) Very rapid Very accurate Semiconservative

  30. Semi conservative

  31. Think about it…. • In the bacteria E.coli the entire genome is replicated in just 40 minutes at a rate of 1000 nucleotides per second. In Eukaryotic cell the rate is 50 nucleotides per second. In which cell do you think there will be more mistakes?

  32. What most likely happens if the DNA makes a mistake during replication and puts a C where a T should be? • It results in a mutation • The cell makes a new protein • The mistake is corrected • DNA replication stops

  33. Mutations and Cancer

  34. Number of New Cases per year Chance of Surviving (%) Pancreatic cancerSilent killer

  35. Cancer • Mutations in cell division/cell grwoth • Caused by multiple genetic mutations • Sometimes they are inherited cancers

  36. Cancer related genes • Proto-oncogenes when mutated become oncogenes • Tumor suppressor genes • DNA repair genes

  37. Cologuard is an noninvasive colon cancer screening test based on stool sample

  38. Frequency of gene mutations in different types of cancer Growth promoting gene called RAS is commonly mutated in cancer cells

  39. Naked mole rat genome sequencedThis is exciting news…Why?

  40. chromosome gene protein One-gene, one-protein hypothesis Codes for

  41. Tumor -Suppressor Genes (“brakes”) Brakes failed!

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