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DNA Replication

DNA Replication


By the end of this tutorial, you should have a general understanding of the process of DNA Replication including:

  1. describe Meselson & Stahl’s experiment and its role in identifying the semi-conservative nature of DNA replication.
  2. describe how the exergonic hydrolysis of nucleotide triphosphates into nucleotide monophosphates are coupled both chemically and thermodynamically to the endergonic synthesis of the ester linkage between the 5’ phosphate (of the incoming nucleotide) to the free 3’ hydroxyl group of the deoxyribose sugar.
  3.     describe DNA replication in terms of:
    • the mitotic/meiotic cycle
    • enzymes involved: DNA polymerase, helicase, ligase, endonuclease, RNA polymerase
    • deoxynucleoside triphosphates
    • 5'-3' synthesis
    • continuous and discontinuous synthesis
    • Okazaki fragments
    • base pairing

           The next tutorial will explore these in more detail.

Once Watson and Crick discovered the structure of DNA the most pressing research question now became to figure out how it replicated. Seminal work from Meselson & Stahl confirmed the semi-conservative nature of DNA replication.  Today, new details are still being uncovered about details of this process.

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This tutorial begins with the work of Meselson & Stahl which verified the semi-conservative replication of DNA. Then an overview outlines the basics of adding trinucleotides to a growing chain. The role of the DNA polymerase complex and primase and the enzymes that open up the DNA double helix are explained with synthesis of the Leading Strand (continuous synthesis) and the Lagging Strand (discontinuous synthesis). Like with chromosomes, the telomere finishes the tutorial.

Source: M. O'Mahony, open source images unless otherwise cited in tutorial

Student Notes Template

Template with Figures for Tutorial 4 on DNA Replication


Source: M. O'Mahony, Open source figures, references as needed by figures.

Meselson & Stahl Experiment

This interactive provides both animations and review activities to explain both Meselson and Stahl's experiment and their verification of the semi-conservative replication of DNA.

...and another from McGraw-Hill.

Source: © 2008 Sinauer Associates, W. H. Freeman & Co., and Sumanas, Inc.

Lagging Strand - DNA Replication

Good, albeit a bit simplistic video of how the lagging strand is synthesized. This, taken with the XXX videos give a good explanation of Lagging Strand synthesis.

Source: Garland Science

Animations of DNA Synthesis

Source: Various - see above

Role of Topoisomerase

Nice summary of how Topoisomerase works with some nice visual analogies.

Source: YouTube

Mismatch Repair

Animation from HHMI Biointeractive  that shows how most errors during replication are fixed.

This is from  lecture one of the 2003 Holiday Lectures Series "Learning From Patients: The Science of Medicine" where it was used to explain how some cancers can get started.

Source: HHMI Biointeractive

Scitable:Molecular Events of DNA Replication

Paper posted on Scitable

Pray, L. (2008) Major molecular events of DNA replication. Nature Education 1(1):99


Source: Sciable -

The Semi-Conservative Replication of DNA

In 1953, Watson and Crick proposed a double-helical structure for DNA and suggested that it replicated in a semi-conservative manner. This method of replication was not universally accepted as correct, however. In this talk, Meselson recalls the events that led him to meet Frank Stahl and to plan and execute the now famous experiment proving that DNA does indeed undergo semi-conservative replication.

Source: iBiology Seminars, American Society of Cell Biology

DNA Replication

Dr. Alberts spent nearly 30 years trying to understand how DNA is replicated. When he began his graduate work in 1961, very little was known about how DNA was copied before each cell division. Alberts describes the key breakthroughs that led to our current understanding of the complex protein machine that drives DNA replication, and he provides some insight on tackling the big problems in biology.  (35 min)

Source: American Society for Cell Biology, iBiology

The Roles of Telomeres and Telomerase

Telomerase, a specialized ribonucleprotein reverse transcriptase, is important for long-term eukaryotic cell proliferation and genomic stability, because it replenishes the DNA at telomeres. Thus, depending on cell type telomerase partially or completely (depending on cell type) counteracts the progressive shortening of telomeres that otherwise occurs. Telomerase is highly active in many human malignancies, and a potential target for anti-cancer approaches. Furthermore, recent collaborative studies have shown the relationship between accelerated telomere shortening and life stress and that low telomerase levels are associated with six prominent risk factors for cardiovascular disease.

Source: American Society for Cell Biology, iBiology

Cell Cycle Animation

OK, it's in Dutch - but the animation is what is really good! 

Source: BIOplek, G.A.M. Scholte and C.M. Marree

Protein Data Bank: DNA Polymerase

Molecule of the Month for March 2000


Source: RCSB Protein Data Bank

Structure and Function of Telomeres

This is an interactive activity that lets you learn about telomeres and how they are involved with DNA replication.


Source: HHMI

Life at the End of the Chromosome: Another RNA Machine

This HHMI Holiday lecture is 58 min long and talks about the telomeres - found at the end of chromosomes.

Source: HHMI

DNA Zip - a game

Go to Spongelab ( ) and search for DNAZip!

DNAZip! is a video game about DNA created for a museum space. When a cell divides in two, its DNA must be copied so that each cell inherits a complete copy of DNA. The DNA helix is unzipped and each half is rezipped with bases (A, C, T, G) floating in the cell. In this game, you play the character Zip to help the protein zipper (DNA polymerase) complete the DNA code. Zip needs to capture the matching base and deliver it to the protein to keep it going. But you need to be quick! Zip needs to figure out the DNA code and navigate platforms made from microtubules and actin filaments before time runs out!

Source: Spongelab