Bloom syndrome (OMIM 210900) is an autosomal recessive disorder caused by mutation of a DNA helicase. Among the principal symptoms of the disease are chromosome instability and a propensity to develop cancer. Explain these symptoms on the basis of the helicase mutation.
Table of contents
- 1. Introduction to Genetics51m
- 2. Mendel's Laws of Inheritance3h 37m
- 3. Extensions to Mendelian Inheritance2h 41m
- 4. Genetic Mapping and Linkage2h 28m
- 5. Genetics of Bacteria and Viruses1h 21m
- 6. Chromosomal Variation1h 48m
- 7. DNA and Chromosome Structure56m
- 8. DNA Replication1h 10m
- 9. Mitosis and Meiosis1h 34m
- 10. Transcription1h 0m
- 11. Translation58m
- 12. Gene Regulation in Prokaryotes1h 19m
- 13. Gene Regulation in Eukaryotes44m
- 14. Genetic Control of Development44m
- 15. Genomes and Genomics1h 50m
- 16. Transposable Elements47m
- 17. Mutation, Repair, and Recombination1h 6m
- 18. Molecular Genetic Tools19m
- 19. Cancer Genetics29m
- 20. Quantitative Genetics1h 26m
- 21. Population Genetics50m
- 22. Evolutionary Genetics29m
8. DNA Replication
Overview of DNA Replication
Problem 27a
Textbook Question
DNA polymerases in all organisms add only 5' nucleotides to the 3' end of a growing DNA strand, never to the 5' end. One possible reason for this is the fact that most DNA polymerases have a proofreading function that would not be energetically possible if DNA synthesis occurred in the 3' to 5' direction.
Sketch the reaction that DNA polymerase would have to catalyze if DNA synthesis occurred in the 3' to 5' direction.

1
Understand the directionality of DNA synthesis: DNA polymerases synthesize DNA by adding nucleotides to the 3' end of the growing strand, which means the strand grows in the 5' to 3' direction. This is due to the chemical structure of nucleotides and the energy dynamics of the reaction.
Review the chemical structure of nucleotides: Each nucleotide consists of a phosphate group, a sugar (deoxyribose), and a nitrogenous base. The phosphate group is attached to the 5' carbon of the sugar, and the hydroxyl (-OH) group is attached to the 3' carbon. DNA polymerase catalyzes the formation of a phosphodiester bond between the 3' hydroxyl group of the growing strand and the 5' phosphate group of the incoming nucleotide.
Consider the energy requirements for synthesis in the 3' to 5' direction: If DNA synthesis occurred in the 3' to 5' direction, the reaction would require the incoming nucleotide to provide a 3' hydroxyl group for bond formation. This would necessitate a different energy source, as the current mechanism relies on the hydrolysis of the high-energy phosphate bonds in the incoming nucleotide triphosphate (dNTP).
Sketch the hypothetical reaction: In the 3' to 5' synthesis direction, DNA polymerase would need to catalyze the formation of a bond between the 5' phosphate group of the growing strand and the 3' hydroxyl group of the incoming nucleotide. This reaction would likely require a new mechanism for energy transfer, as the current proofreading function relies on the ability to remove mismatched nucleotides from the 3' end, which would not be possible in this scenario.
Reflect on the implications for proofreading: The proofreading function of DNA polymerase depends on the ability to excise mismatched nucleotides from the 3' end of the growing strand. If synthesis occurred in the 3' to 5' direction, removing a mismatched nucleotide would leave a free 5' end, which lacks the high-energy phosphate bonds needed to drive further synthesis. This would make proofreading energetically unfavorable and compromise the fidelity of DNA replication.

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Key Concepts
Here are the essential concepts you must grasp in order to answer the question correctly.
DNA Polymerase Function
DNA polymerases are enzymes responsible for synthesizing new DNA strands by adding nucleotides to the growing chain. They can only add nucleotides to the 3' end of a DNA strand, which means that DNA synthesis occurs in a 5' to 3' direction. This unidirectional synthesis is crucial for maintaining the integrity of the genetic information during replication.
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Proofreading Mechanism
Many DNA polymerases possess a proofreading function that allows them to correct errors during DNA synthesis. This mechanism involves the enzyme's ability to detect and remove incorrectly paired nucleotides. If DNA synthesis were to occur in the 3' to 5' direction, the proofreading process would be less efficient and energetically unfavorable, potentially leading to a higher rate of mutations.
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Directionality of DNA Synthesis
The directionality of DNA synthesis is a fundamental aspect of molecular biology. DNA strands have polarity, with a 5' phosphate group and a 3' hydroxyl group. The requirement for DNA polymerases to synthesize DNA in the 5' to 3' direction ensures that the newly added nucleotides can form the necessary phosphodiester bonds, which are critical for the stability and continuity of the DNA molecule.
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