1. Copyright © 2009 Pearson Education, Inc. Chapter 10 DNA Replication and Recombination

2. Copyright © 2009 Pearson Education, Inc. Telomeres, Aging, and Cancer Learn Genetics – Telomeres FISH for telomeres: Highlighting the ENDS of the chromosomes.

3. Copyright © 2009 Pearson Education, Inc. Telomeres, Aging, and Cancer http://learn.genetics.utah.edu/content/chromoso mes/telomeres/ COPY the web address above and READ information on your device or on a laptop. IN ADDITION, Make sure you have read information on TELOMERES in your text, page 221.

4. Copyright © 2009 Pearson Education, Inc. What are Telomeres? Stretches of DNA Protect our genetic code Allow for cells to divide Similar to the plastic tips on shoelaces Keep chromosome ends from fraying and sticking to each other

5. Copyright © 2009 Pearson Education, Inc. What Happens to Telomeres When Cells Divide? Each time a cell divides the telomeres get shorter. It is a bit shorter than the original strand because of the room needed at the end for the RNA primer used during replication. When they get too short, the cell can no longer divide The cell becomes senescent or it dies.

6. Copyright © 2009 Pearson Education, Inc. What is Telomerase? An enzyme that adds bases to the ends of telomeres. Telomerase keeps telomeres from wearing down too much. As we age there is not enough telomerase, so the telomeres grow shorter and the cells age. Telomerase remains active in sperm and eggs, but slowly loses effect through fetal development.

7. Copyright © 2009 Pearson Education, Inc. Telomeres and Cancer As cells divide more often during cancer, telomeres can become very short. If they are too short, the cell dies. Some cancers produce telomerase as a way to stay alive and continue to divide. Scientists are trying to stop telomerase activity in some cancers as a way to treat the cancer and force cell death.

8. Copyright © 2009 Pearson Education, Inc. Telomeres and Aging Shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease. Scientists have been able to use telomerase in the lab to keep human cells dividing far beyond their normal limit, and the cells do not become cancerous.

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10. Copyright © 2009 Pearson Education, Inc. Chapter Contents 10.1DNA Is Reproduced by Semiconservative Replication 10.2DNA Synthesis in Bacteria Involves Five Polymerases, as well as Other Enzymes 10.3Many Complex Tasks Must Be Performed during DNA Replication 10.4A Summary of DNA Replication in Prokaryotes 10.5Replication in Prokaryotes Is Controlled by a Variety of Genes Continued

11. Copyright © 2009 Pearson Education, Inc. 10.6Eukaryotic DNA Synthesis Is Similar to Synthesis in Prokaryotes, but More Complex 10.7Telomeres Provide Structural Integrity at Chromosome Ends but are Problematic to Replicate 10.8DNA Recombination, Like DNA Replication, Is Directed by Specific Enzymes 10.9Gene Conversion Is a Consequence of DNA Recombination

12. Copyright © 2009 Pearson Education, Inc. The complementarity of DNA strands allows each strand to serve as a template for synthesis of the other. (Figure 10.1) Section 10.1: DNA Is Reproduced by Semiconservative Replication

13. Copyright © 2009 Pearson Education, Inc. Three possible modes of DNA replication are possible: conservative semiconservative dispersive (Figure 10.2) Section 10.1

14. Copyright © 2009 Pearson Education, Inc. Figure 11.2

15. Copyright © 2009 Pearson Education, Inc. The Meselson-Stahl experiment demonstrated that: DNA replication is semiconservative each new DNA molecule consists of one old strand and one newly synthesized strand (Figure 10.3 and Figure 10.4) Section 10.1

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18. The Taylor-Woods-Hughes experiment demonstrated that DNA replication is semiconservative in eukaryotes (Figure 10.5) Section 10.1

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22. DNA REPLICATION AS A SEMICONSERVATIVE PROCESS

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24. DNA Replication Enzymes EnzymeFunction in DNA replication DNA HelicaseUnwinds the DNA double helix at the Replication Fork.Replication Fork DNA Polymerase Builds a new DNA strand by adding nucleotides in the 5' to 3' direction. Also performs proof-reading and error correction. DNA clamp A protein which prevents DNA polymerase III from unattaching from the DNA parent strand. TopoisomeraseTopoisomerase/ DNA Gyrase DNA Gyrase Relaxes the DNA from its super-coiled nature/Relieves strain of unwinding by DNA helicase. DNA Ligase Re-anneals the semi-conservative strands and joins Okazaki Fragments of the lagging strand.Okazaki Fragments Primase Provides a starting point for DNA polymerase to begin synthesis of the new DNA strand. Telomerase Lengthens telomeric DNA by adding repetitive nucleotide sequences to the ends of eukaryotic chromosomes.eukaryotic chromosomes

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26. QUICK Overview: Major Elements: Segments of single-stranded DNA are called template strands. Gyrase (a type of topoisomerase) relaxes the supercoiled DNA. Initiator proteins and DNA helicase binds to the DNA at the replication fork and untwist the DNA using energy derived from ATP (adenosine triphosphate). (Hydrolysis of ATP causes a shape change in DNA helicase) DNA primase next binds to helicase producing a complex called a primosome (primase is required for synthesis), Primase synthesizes a short RNA primer of 10-12 nucleotides, to which DNA polymerase III adds nucleotides. Polymerase III adds nucleotides 5’ to 3’ on both strands beginning at the RNA primer. The RNA primer is removed and replaced with DNA by polymerase I, and the gap is sealed with DNA ligase. Single-stranded DNA-binding (SSB) proteins (>200) stabilize the single-stranded template DNA during the process.

27. Copyright © 2009 Pearson Education, Inc. DNA replication is continuous on the leading strand and discontinuous on the lagging strand: Unwinding of any single DNA replication fork proceeds in one direction. The two DNA strands are of opposite polarity, and DNA polymerases only synthesize DNA 5’ to 3’. Solution: DNA is made in opposite directions on each template. Leading strand synthesized 5’ to 3’ in the direction of the replication fork movement. continuous requires a single RNA primer Lagging strand synthesized 5’ to 3’ in the opposite direction. semidiscontinuous (i.e., not continuous) requires many RNA primers, DNA is synthesized in short fragments.

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30. Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings. Fig. 3.5 - Model of DNA replication

31. Copyright © 2009 Pearson Education, Inc. Peter J. Russell, iGenetics: Copyright © Pearson Education, Inc., publishing as Benjamin Cummings. Fig. 3.5 - Model of DNA replication

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33. Concepts and terms to understand: Why are gyrase and helicase required? The difference between a template and a primer? The difference between primase and polymerase? What is a replication fork and how many are there? Why are single-stranded binding (SSB) proteins required? How does synthesis differ on leading strand and lagging strand? Which is continuous and semi-discontinuous? What are Okazaki fragments? How do polymerase I and III differ?