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The Molecular Basis for Inheritance

The Molecular Basis for Inheritance. Genes to Proteins Chapter 16. Oswald Avery. Oswald Avery Maclyn McCarty Colin McLeod. 1944. 1952, Alfred Hershey and Martha Chase. Bacteria phages on a bacteria. Erwin CHargaff. Erwin Chargaff. DNA Replication.

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The Molecular Basis for Inheritance

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  1. The Molecular Basis for Inheritance Genes to Proteins Chapter 16

  2. Oswald Avery Oswald Avery Maclyn McCarty Colin McLeod 1944

  3. 1952, Alfred Hershey and MarthaChase

  4. Bacteria phages on a bacteria

  5. Erwin CHargaff Erwin Chargaff

  6. DNA Replication • Replication begins at specific sites on the DNA origins of replication. • Helicase, single stranded binding protein and topoisomerase are involved. • Replication proceeds in both directions creating a “bubble” of replication along the strand. • There may be many areas of simultaneous replication reducing the time needed for completion, eventually merging into a completed strand.

  7. Elongation of new strand • DNA polymerase catalyses the elongation at the replication fork. • DNA polymerase adds the nucleotides, one by one, to the growing end of the new strand. • There are 11 different polymerases involved in eukaryotic cells, adding 50 nucleotides/sec.

  8. Antiparallel Elongation • DNA polymerase adds nucleotides ONLY at the free 3’ end of the growing strand. • DNA can only elongate in the 5’-3’ direction • This results in a leading and lagging strand.

  9. Leading Strand • DNA polymerase III begins elongation on the original 3’ end of the DNA and adds continuously as the replication fork progresses to the end.

  10. Lagging Strand • To elongate the other strand, DNA polymerase III must work along the template in a direction away from the replication fork. • The lagging strand is replicated in a series of segments at each replication bubble. • OKAZAKI fragments are about 100-200 nucleotides long. • DNA Ligase joins the fragments together and binds to the sugar-phosphate backbone.

  11. Priming DNA segments • DNA polymerases cannot initiate synthesis, they can only add at the 3’ end of an already existing chain that is based paired with the template strand. • An enzyme called a primase can initiate a RNA strand from scratch. • Primase joins RNA nucleotides together, making a primer complementary to the template strand at the location where the initiation of the new DNA will occur.

  12. The primase initiates the production of a primer with a free 3’ end. • DNA polymerase III then adds DNA nucleotides on the free 3’ end of the primer and continues adding to the growing DNA strand. • Only one primer is needed for initiation of the leading strand, yet each Okazaki fragment must be primed separately.

  13. DNA polymerase I replaces the RNA nucleotides of the primers with DNA versions onto the 3’ end of the adjacent Okazaki fragment. • DNA polymerase I cannot join the final nucleotide of the replacement DNA segment to the first nucleotide of the Okazaki fragment whose primer was just replaced. • DNA ligase joins fragments together and binds to the backbone.

  14. Animation link for replication

  15. Repair Ware • Although the errors in completed DNA are 1/10 billion, pairing errors between incoming nucleotides are 100,000x more common. • Polymerase proofreads each nucleotide against its template as soon as it is added. • Sometimes mismatched nucleotides evade proofreading by the polymerase or arise after synthesis takes place

  16. DNA can be damaged by environment and occasionally undergo spontaneous chemical changes under normal chemical conditions. • Each cell continuously monitors and repairs its genetic material. • A Nuclease is used to “cut out” the damaged section of DNA and the resultant gap is filled with the proper nucleotides Nucleotide excision repair. ie. Xeroderma pimentosum

  17. Replicating Ends of the DNA • Despite the repair ware available to the cell there is a small portion of the DNA that the polymerase is unable to replicate or repair. • Because the polymerase can only add nucleotides to the 3’ end of a pre-existing template, the machinery provides no way to complete the 5’ ends of the daughter DNA.

  18. Eukaryotic cells contain telomere ends. • In humans,telomeres are a “TTAGGG” repeat between 100 to 1000 times. • Telomeric DNA protects the organisms genes from erosion through successive rounds of DNA replication. • Telomeres and specific proteins prevent the staggered ends of the daughter molecule from activating repair ware.

  19. Germ cells that give rise to gametes contain telomerase that catalyze the lengthening of the telomeres. • Telomerase is not active in somatic cells but provided maximum length to the cells of the zygote.

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