Slide 1

  • Topic: Genetics and Evolution
  • Subtopic: Molecular Basis of Inheritance - Elongation of Nucleotide chain

Slide 2

  • DNA replication is the process of making an identical copy of DNA molecules.
  • It occurs during the S phase (Synthesis phase) of the cell cycle.
  • The enzyme responsible for DNA replication is DNA polymerase.
  • DNA replication is semiconservative, meaning each new DNA molecule has one original (parental) strand and one new (daughter) strand.
  • The process of DNA replication involves several steps.

Slide 3

  • Step 1: Initiation

    • DNA helicase unwinds the DNA double helix by breaking hydrogen bonds between the nitrogenous bases.
    • Replication fork is formed where the DNA strands separate.

  • Step 2: Elongation

    • DNA polymerase adds new nucleotides to the 3’ end of the growing DNA strand.
    • It follows the complementary base-pairing rule (A with T and G with C).

  • Step 3: Termination

    • DNA replication is completed when the entire DNA molecule is replicated.
    • Replication forks converge and the process is terminated.

Slide 4

  • Leading Strand Synthesis
    • The leading strand is synthesized continuously in the 3’ to 5’ direction.
    • DNA polymerase adds nucleotides to the leading strand as it unwinds.
    • It continuously synthesizes a complementary strand from the initial point of replication.
  • Lagging Strand Synthesis
    • The lagging strand is synthesized discontinuously in the 5’ to 3’ direction.
    • DNA polymerase synthesizes short Okazaki fragments.
    • DNA ligase joins the Okazaki fragments to form a continuous strand.

Slide 5

  • DNA Replication Errors
    • DNA polymerase has a proofreading activity that helps to correct errors in replication.
    • However, errors can still occur leading to mutations.
    • Mutations can be harmful, neutral, or beneficial.
    • Mutations can lead to genetic variation, which is important for evolution.
  • Example: Sickle Cell Anemia
    • Sickle cell anemia is a genetic disorder caused by a mutation in the β-globin gene.
    • This mutation results in the production of abnormal hemoglobin, causing red blood cells to become sickle-shaped.
    • Sickle cell anemia is an example of a harmful mutation.

Slide 6

  • Telomeres and Telomerase

    • Telomeres are repetitive sequences of DNA at the ends of chromosomes.
    • They protect the coding regions of genes from getting damaged during DNA replication.
    • Telomeres shorten with each round of DNA replication, leading to cellular aging.

  • Telomerase

    • Telomerase is an enzyme that adds repetitive DNA sequences to the ends of chromosomes.
    • It helps to maintain telomere length and prevents loss of genetic material.
    • Telomerase is highly active in germ cells, stem cells, and cancer cells.

Slide 7

  • Importance of DNA Replication

    • DNA replication is essential for cell division and growth.
    • It ensures the accurate transmission of genetic information from one generation to the next.
    • Without DNA replication, new cells would not have the necessary genetic material to function properly.

  • Role of DNA Replication in Evolution

    • DNA replication, along with mutation and natural selection, plays a crucial role in evolution.
    • Genetic variation resulting from DNA replication errors and mutations provides the raw material for natural selection to act upon.

Slide 8

  • Applications of DNA Replication
    • DNA replication is widely used in various fields, including:
      • Biotechnology: DNA replication is used in genetic engineering to produce recombinant DNA molecules.
      • Forensics: DNA replication is used in DNA profiling for identification purposes.
      • Medicine: Understanding DNA replication helps in the development of targeted therapies for genetic diseases.
  • Example: Polymerase Chain Reaction (PCR)
    • PCR is a technique used to amplify specific DNA sequences.
    • It relies on DNA replication to generate millions of copies of a specific DNA region.
    • PCR has revolutionized genetic research, diagnostics, and forensic investigations.

Slide 9

  • Summary
    • DNA replication is a crucial process that ensures the accurate transmission of genetic information.
    • It involves multiple steps and enzymes, with DNA polymerase being the key enzyme responsible for adding new nucleotides.
    • DNA replication is semiconservative and occurs during the S phase of the cell cycle.
    • Errors in DNA replication can lead to mutations, which can be harmful, neutral, or beneficial.
    • DNA replication plays a vital role in evolution, genetic variation, and various applications.

Slide 10

  • References:
    • Nelson, D.L., Cox, M.M. Lehninger Principles of Biochemistry. W.H. Freeman and Company, 2013.
    • Lodish, H., Berk, A., Zipursky, S.L., et al. Molecular Cell Biology. W.H. Freeman and Company, 2000.
    • Campbell, N.A., Reece, J.B., Urry, L.A., et al. Biology. Pearson, 2020.

Slide 11

  • Features of DNA Replication
    • Bidirectional: Replication occurs in both directions from the origin of replication.
    • Semidiscontinuous: Leading strand is synthesized continuously, while lagging strand is synthesized discontinuously.
    • Semi-conservative: Each newly synthesized DNA molecule consists of one original strand and one newly synthesized strand.
    • Highly accurate: Proofreading activities of DNA polymerase help ensure fidelity of replication.
    • Rapid: Replication occurs at a rate of about 50 nucleotides per second in humans.
  • Example: DNA Replication in E. coli
    • DNA replication in E. coli is well-studied and serves as a model for understanding the process.
    • The replication of the E. coli chromosome initiates at a single origin of replication, called OriC.
    • Multiple replication forks are formed, allowing for efficient and rapid replication.

Slide 12

  • DNA Replication Step 1: Initiation
    • Initiation factors recognize and bind to the origin of replication.
    • DNA helicase unwinds the DNA double helix, creating the replication fork.
    • Single-stranded binding proteins stabilize the separated DNA strands.
    • Topoisomerases relieve the strain caused by unwinding the DNA.
  • DNA Replication Step 2: Elongation
    • Primase synthesizes a short RNA primer complementary to the DNA template strand.
    • DNA polymerase adds nucleotides to the 3’ end of the RNA primer, creating a DNA chain.
    • Leading strand is continuously synthesized in the 3’ to 5’ direction.
    • Lagging strand is synthesized discontinuously in the form of Okazaki fragments.

Slide 13

  • DNA Replication Step 3: Termination
    • As the replication forks meet, a termination region is reached.
    • Termination proteins facilitate the completion of replication.
    • DNA ligase joins the Okazaki fragments on the lagging strand, creating a continuous DNA strand.
  • Replisome
    • The replisome is a multi-protein complex involved in DNA replication.
    • It coordinates the activities of various enzymes required for replication.
    • The replisome consists of DNA polymerase, helicase, primase, and other accessory proteins.

Slide 14

  • DNA Replication in Eukaryotes
    • Eukaryotic DNA replication is similar to prokaryotic replication but more complex.
    • Eukaryotic genomes are larger and contain multiple origins of replication.
    • Replication occurs in discrete units called replication forks or replication bubbles.
    • Telomeres and telomerase play important roles in eukaryotic DNA replication.
  • Example: Telomeres in Eukaryotes
    • Telomeres are repetitive DNA sequences at the ends of eukaryotic chromosomes.
    • They protect the essential genetic material from being lost during replication.
    • Telomerase helps to maintain telomere length, preventing degradation and chromosome fusion.

Slide 15

  • Regulation of DNA Replication
    • DNA replication is tightly regulated to ensure accurate and timely replication.
    • Various checkpoints and regulatory proteins control the initiation and progression of replication.
    • Cyclins and cyclin-dependent kinases (CDKs) play crucial roles in cell cycle control and DNA replication.
  • Example: Cyclin-CDK Complexes
    • Cyclins are proteins that oscillate in concentration throughout the cell cycle.
    • CDKs are enzymes that are activated by cyclins.
    • Cyclin-CDK complexes phosphorylate target proteins involved in DNA replication, ensuring proper timing and coordination.

Slide 16

  • DNA Replication Errors and Repair Mechanisms
    • Despite the accuracy of DNA replication, errors can occur.
    • DNA polymerase has a proofreading activity to correct mismatched base pairs.
    • Mismatch repair, nucleotide excision repair, and other mechanisms exist to fix replication errors.
  • Example: Mismatch Repair
    • Mismatch repair is a DNA repair mechanism that corrects base-pairing errors.
    • Mismatch repair proteins detect and remove the mismatched nucleotide.
    • The gap is filled with the correct nucleotide, and the DNA is ligated.

Slide 17

  • Telomeres and Aging
    • Telomeres shorten with each round of DNA replication.
    • Reduction in telomere length is associated with cellular aging.
    • Eventually, telomeres become critically short, leading to cell cycle arrest or cell death.
  • Telomerase and Cancer
    • In most somatic cells, telomerase is not active, resulting in telomere shortening.
    • Telomerase is reactivated in most cancer cells, enabling unlimited replication and cell survival.
    • Inhibition of telomerase activity is a potential target for cancer therapies.

Slide 18

  • DNA Replication and Antibiotics
    • Antibiotics can interfere with DNA replication in bacteria, leading to inhibition of bacterial growth.
    • Some antibiotics target enzymes involved in DNA replication, such as DNA gyrase or topoisomerases.
    • Understanding the mechanisms of DNA replication has helped in the development of antibiotics.
  • Example: Fluoroquinolones
    • Fluoroquinolones are a class of antibiotics that inhibit bacterial DNA gyrase, an enzyme involved in DNA replication.
    • By targeting DNA gyrase, fluoroquinolones prevent DNA supercoiling and replication.
    • Fluoroquinolones are commonly used to treat bacterial infections.

Slide 19

  • Applications of DNA Replication Studies
    • Understanding DNA replication has numerous practical applications:
      • Genetic testing: DNA replication helps in sequencing and identifying genetic variations associated with diseases.
      • Pharmacology: Knowledge of DNA replication aids in the development of antiviral drugs targeting viral replication.
      • Synthetic biology: DNA replication studies contribute to the design and construction of synthetic DNA molecules.
  • Example: DNA Sequencing
    • DNA replication serves as a basis for various DNA sequencing technologies.
    • Next-generation sequencing techniques rely on the ability to amplify and sequence DNA accurately.

Slide 20

  • Summary
    • DNA replication is a complex process that ensures accurate transmission of genetic information.
    • It involves multiple steps, enzymes, and regulatory mechanisms.
    • DNA replication is bidirectional, semidiscontinuous, and highly accurate.
    • Eukaryotic DNA replication is more complex and involves multiple origins of replication.
    • Telomeres, telomerase, and regulatory proteins play important roles in DNA replication.
    • Understanding DNA replication has practical implications in medicine, biotechnology, and genetic research.
  • Questions?
  • Discussion

Sorry, but I can’t generate that story for you.