Teaching the Concept of DNA Replication and Repair: A Summary
By: Jessica Joseph and Sunita Bali
Curriculum Expectations Addressed (Grade 12: Molecular Biology)
Overall Expectations
D2. investigate, through laboratory activities, the structures of cell components and their roles
in processes that occur within the cell;
D3. demonstrate an understanding of concepts related to molecular genetics, and how genetic
modification is applied in industry and agriculture.
Specific Expectations
D2.2 analyse a simulated strand of DNA to determine the genetic code and base pairing of DNA
(e.g., determine base sequences of DNA for a protein; analyse base sequences in DNA to
recognize an anomaly) [AI]
D3.1 explain the current model of DNA replication, and describe the different repair
mechanisms that can correct mistakes in DNA sequencing
Lesson Sequence
The lessons may be organized in the following way:
Lesson 1: Discovery of DNA: A Review
 Scientists and Experiments leading to the Discovery of DNA
Lesson 2: DNA Structure: A Review
 The Chemical Composition of DNA, The Double Helix
Lesson 3: DNA Replicates Semi-Conservatively
 The Meselson and Stahl Experiment
Lesson 4: The Process of DNA Replication
 Separating the DNA Strands, Building the Complementary Strands, DNA Repair
Lesson 5: Differentiated Assessment
 Using stations based on multiple-intelligences to assess student learning
Background Information: DNA Replication and Repair
DNA (Deoxyriboucleic acid) is an incredible molecule that forms the basis of life on
Earth. DNA molecules contain instructions for building every living organism on Earth, from the
tiniest bacterium to a massive blue whale. DNA also has the ability to replicate, or make copies
of itself. This allows living things to grow and reproduce.
Cells are capable of giving rise to a new generation of cells by undergoing DNA
replication and cell division. During cell division in eukaryotic cells, the replicated genetic
material in the nucleus is divided equally between two daughter nuclei in a process known as
mitosis. This is usually followed by cytokinesis, in which the cell is split into two new cells.
Mitotic cell division is essential for the growth of tissues during embryonic development and
childhood, as well as for tissue regeneration, such as the continuous, daily replacement of
thousands of skin cells or the repair of damaged tissue.
It is important that each daughter cell has an exact copy of the parent cell’s DNA. DNA is
a macro-molecule that consists of repeating units, called nucleotides. Nucleotides are made up
of a sugar molecule, a phosphate and one out of four nitrogenous bases (Adenine, Thymine,
Guanine, Cytosine). DNA is always found as double chains of nucleotides forming a structure
that resembles that of a twisted ladder. Repeating sugar and phosphate molecules are forming
the sides or backbone of the ladder and pairs of bases the rungs of the ladder. Adenine always
pairs with Thymine and Guanine always pairs with Cytosine (A-T, C-G); they are complimentary
base pairs. Consequently there are always as many "A's" than there are "T's" in a DNA molecule
and equal numbers of "C's" and "G's" (Chargaff rule). When cells divide, they have to copy the
genetic information and pass on one copy to each daughter cell. DNA replication is "semiconservative"; the DNA double helix unravels and unzips (the weak hydrogen bonds between
the bases are broken). Each original DNA strand now serves as a template for the new strand.
Free-floating nucleotides that are made in other parts of the cell match with their
complimentary nucleotide "partner" and link up. In this way, a single DNA molecule becomes
two. One strand of each of the two DNA molecules is the original (conserved), and one strand is
freshly assembled (hence: Semi (half) conservative replication).
Advance Preparation/Teaching Ideas
Lesson 1
Many scientists contributed to the understanding of DNA location, structure and
composition. This information can be reviewed through using Powerpoint to present multiple
choice questions that students answer using clickers.
In order to assess student knowledge, they will be asked to complete a DNA timeline
scavenger hunt online at http://www.dnai.org/timeline/index.html. The student worksheet
found at http://www.dnai.org/teacherguide/guide.html.
Lesson 2
Before teaching students about DNA replication and repair, it is important to review
the composition and structure of DNA. This review can be performed by showing students a
video summary of DNA Structure (You Tube:
http://www.youtube.com/watch?v=ZGHkHMoyC5I). This video may be shown through a
projector or on a SMARTBoard.
Once this video is shown, the students will be divided into pairs in order to perform
Activity # 1 (see at the bottom). After the activity is completed, the teacher should have a class
discussion using the questions mentioned in the activity.
Lesson 3
The teacher will begin by showing students a figure of semi-conservative,
conservative and dispersive replication. Students will be asked to explain the difference. An
overhead projector and figure transparencies will be used to explain the experiment to the
students.
The Meselson and Stahl Experiment
In order to show that DNA replicated semi-conservatively, an experiment was
conducted by Matthew Meselson and Franklin Stahl in 1958.
 In this experiment, bacterial cells (E. Coli) were grown for several generations on a medium
containing a heavy isotope of nitrogen (15N). The DNA (nitrogenous bases) in these cells
therefore contained “heavy” nitrogen.
 The cells were then transferred to a new medium containing the normal lighter isotope
(14N). At various times after the transfer, samples of the bacteria were collected.
 The DNA was then extracted from the bacteria and dissolved in a solution of cesium
chloride.
 The samples were then spun rapidly in a centrifuge. When the cesium chloride is centrifuged
at high speed, a concentration gradient is established in the tube. DNA molecules move in a
gradient until they reach a place where their density equals that of cesium.
 DNA containing 14N moved to a position in the gradient determined by its density. DNA
containing 15N is denser than that containing 14N, so it sank to a lower position in the
cesium gradient.
 After one generation in the 14N medium, the bacteria yielded a single band of DNA with a
density between that of 14N-DNA and 15N-DNA, indicating that only one strand of each
duplex contained 15N.

After two generations in the 14N medium, two bands were obtained, one with intermediate
density (in which one of the strands contained 15N) and one of low density (in which neither
strand contained 15N).
 Meselson and Stahl concluded that replication of the DNA duplex involves building new
molecules by separating parent strands and then adding new nucleotides to form the
complementary strand on each of these templates.
Once the experiment has been explained, student will be shown an animation
(http://highered.mcgraw-hill.com/olc/dl/120076/bio22.swf) to make the concept clear.
The teacher will divide the students into pairs to complete a virtual lab
(http://www.sumanasinc.com/webcontent/animations/content/meselson.html). The students
will be assessed through Quiz # 1 (see at the bottom).
Lesson 4
The teacher will quickly review DNA structure and composition by asking questions
such as “What forms the backbone of DNA?”, “Which bases bind with each other?”, “What is
meant by antiparallel strands?”, “What kind of bond joins base pairs?”, etc. Once all the
concepts have been reviewed, the teacher will draw a replication fork on the blackboard (Use
different coloured chalk for old and new strands). The teacher will draw in the necessary
enzymes and explain the unwinding of DNA strands and building of complementary strands.
1) DNA replication is complicated and involves many enzymes. It begins when the enzyme
helicase breaks the hydrogen bonds holding the two complementary parent strands together,
resulting in an unzipped helix that terminates at the replication fork.
2) The enzyme gyrase relieves any tension from the unwinding of the double helix.
3) Single-stranded binding proteins (SSBs) anneal to the newly exposed template strands,
preventing them from reannealing.
4) The enzyme primase lays down RNA primers that will be used by DNA polymerase III as a
starting point to build the new complementary strands.
5) DNA polymerase III adds the appropriate deoxyribonucleoside triphosphates to the 3’ end of
the new strand using the template strand as a guide. The energy in the phosphate bonds is used
to drive the process. The leading strand is built continuously toward the replication fork.
At this point, the teacher will draw a second figure to explain that synthesis of the lagging strand
is different because DNA polymerase III only adds new bases in the 5’ to 3’ direction.
Since DNA is always synthesized in the 5’ to 3’ direction and the template strands run
antiparallel, only one strand is able to be built continuously. This strand, which uses the 3’ to 5’
template strand as its guide, is called the leading strand and is built toward the replication fork.
The other strand is synthesized discontinuously in short fragments in the opposite direction to
the replication fork and is known as the lagging strand. Primers are continuously added as the
replication fork forms along the DNA parent strand, and DNA polymerase III builds in short
segments known as Okazaki fragments. DNA polymerase I removes the RNA primers from the
leading strand and fragments of the lagging strand and replaces them with the appropriate
deoxyribonucleotides. Since the lagging strand is built in short segments, another enzyme, DNA
ligase, joins the Okazaki fragments into one strand by creation of a phosphodiester bond. As the
two new strands of DNA are synthesized, two double-stranded DNA molecules are produced
that automatically twist into a helix.
The teacher will now ask students what could happen if there is a mistake in base-pairing.
Students are asked to predict which enzymes learnt about so far may act as proofreaders. The
need and mechanism of DNA repair is explained.
As complementary sequences are built, DNA polymerase III and DNA polymerase I act as quality
control checkers by proofreading the newly synthesized strand. When mistakes occur, either
enzyme can function as an exonuclease. The enzyme backtracks past the nucleotide on the end
of the strand that is incorrectly paired to a nucleotide on the template, excises it, and continues
adding nucleotides to the complementary strand. The repair must be made immediately to
avoid the mistake from being copied in subsequent replications. Errors missed by proofreading
can be corrected by one of several repair mechanisms that operate after the completion of DNA
replication.
To bring everything together, students will be shown the following animations:
- DNA Replication Fork: http://highered.mcgraw-hill.com/olc/dl/120076/micro04.swf
- How Nucleotides Are Added in DNA Replication: http://highered.mcgrawhill.com/olc/dl/120076/bio23.swf
Finally, students will be guided in performing a DNA role-play activity using the following
directions:
 You represent a nucleotide.
 Choose a partner. This person will be your conjugate base.
 Hydrogen bond with your partner using your right hand (shaking hands).
 All sets of partners line up side by side. Each person places their left hand on the right
shoulder of the person beside them. This represents a phosphodiester bond.
 At each end of the line of students there will be one free left hand. This represents the
phosphate group.
 Unzip the DNA strand by breaking your handshakes (hydrogen bonds).
 The rest of the students join in to form complementary strands using the same rules as
above.
Lesson 5
This last lesson will be for assessing student learning. The class will be set up into
the following stations that students will go around in pairs to complete and hand-in:
1) Visual: Students will make a sketch or diagram of the process of DNA replication. (K/I)
2) Musical: Students will listen to the DNA replication song and write another verse for the song.
(K/I/C/A)
http://www.youtube.com/watch?v=dIZpb93NYlw
3) Kinesthetic: Students will design an explanation for DNA replication using body/hand actions.
(K/I/C/A)
4) Linguistic: Students will imagine being a DNA molecule and write a story explaining how they
are copied. (K/I/C)
5) Intrapersonal: Students will write explaining what they found to be fascinating about DNA
replication. (K/I/C/A)
6) Interpersonal: Students will explain their understanding of DNA replication to their partners.
(K/I/C)
7) Logical: Students will perform the DNA replication gizmo at
http://www.explorelearning.com/index.cfm?method=cResource.dspDetail&ResourceID=439
Students will be given a copy of the ‘Student Exploration Sheet’ found on the website. (K/I/C/A)
Summative Assessment will take place at the end of the genetics unit in the form of a Unit Test.
Potential Student Difficulties and Possible Solutions
The students may find it difficult to understand the procedure and conclusions of the Meselson
and Stahl experiment
• Explain each step in detail using illustrations and drawings
The students may have a difficult time visualizing the concept of DNA replication
• Show the animations multiple times
The students may have difficulty keeping track of all the enzymes involved in replication
• Create a word wall with all the important terms
The students may get confused about the lagging strand replication
• Emphasize that DNA strands are antiparallel and DNA polymerase III synthesizes
only in the 5’ to 3’ direction.
Use the following tutorial to reiterate concepts:
http://www.wiley.com/college/pratt/0471393878/student/animations/dna_replication/index.h
tml
Applications and Societal Issues/Implications
DNA analysis can be used to:
• Solve crimes (homicide)
• Identify human remains (missing persons, disasters)
• Determine relationship between family members (paternity, child abductions)
• Medical Research (genetic diseases, drugs)
• Agriculture and Horticulture (genetically modified organisms)
• Animal Husbandry (genetically modified animals)
Accommodations for Special Needs and English language learners
 Model building, role play and animations will help the entire class including ELL and
special needs students to visualize the abstract structure of DNA.
 Posting a word wall with the new vocabulary related to DNA structure and replication
process will help the ELLs and special need students in writing tasks.
 Extra attention and time will be given to ELLs and special needs students during
classroom discussions and in computer lab.
 Peer assistant will be encouraged in the classroom assignments by heterogeneous
grouping of students.
Annotated References/Annotated Internet Addresses
Thomson Nelson Limited. (2003). Biology 12. Toronto, Ontario: Author.
This textbook was the source for background information and was also used for organizing the
lessons.
http://www.accessexcellence.org/RC/AB/WYW/wkbooks/SFTS/activity2.php
This website was used to form Activity # 1 that is used in reviewing DNA composition and
structure.
http://highered.mcgraw-hill.com/olc/dl/120076/bio22.swf
This animation was used to explain the Meselson and Stahl Experiment.
http://www.sumanasinc.com/webcontent/animations/content/meselson.html
This virtual lab was used as assessment for the Meselson and Stahl Experiment.
http://highered.mcgraw-hill.com/olc/dl/120076/micro04.swf
http://highered.mcgraw-hill.com/olc/dl/120076/bio23.swf
These animations were used in summarizing DNA Replication
http://www.youtube.com/watch?v=dIZpb93NYlw
This video shows the DNA replication song that was part of assessment.
http://www.explorelearning.com/index.cfm?method=cResource.dspDetail&ResourceID=439
This gizmo was used as an assessment tool at the end of the lessons.
http://www.wiley.com/college/pratt/0471393878/student/animations/dna_replication/index.h
tml
This tutorial was used to clear any student misconceptions and reiterate the whole process of
DNA replication
Activity # 1
Objective
Students will build a model of DNA.
Materials
DNA patterns (4 for each pair)
Paper
Pencil
Scissors
Preparation
Create and duplicate sample patterns of the follow-ing parts of the DNA molecule: the
four bases (A, C, T, G), a sugar (S), and a phosphate (P).
Instructions
1. Ask students to use the DNA patterns to trace and cut out 16 each of sugar and
phosphate, and 8 of each base.
2. Have students build a model of a segment of a DNA molecule. The segment should
contain 8 base "rungs." Any bases can be used for the sequence, as long as the
appropriate complementary bases are used for the pairs.
Discussion Questions
1) Define the following terms: nucleotide, complementary base pairing, phosphodiester
bond, and glycosyl bond.
2) In a DNA molecule, a purine pairs with a pyrimidine. If this is the case, then why can’t
A–C and G–T pairs form?
3) The following is a segment taken from a strand of DNA: 5’–ATGCCTTA–3’. Write
out the complementary strand for this segment. Be sure to show directionality.
4) What does it mean when we say that the two DNA strands are “antiparallel”
5) Differentiate between a purine and a pyrimidine.
6) How does the structure of a DNA molecule help account for the great variety of life
that exists on earth?
7) Predict how this DNA molecule can be replicated (copied).
Quiz # 1 (Meselson and Stahl Experiment)
Names:_______________________
1) Matthew Meselson and Franklin Stahl observed a total of three bands (heavy, light,
and intermediate) in the density gradient they obtained in their experiment. At which
point in their experiment did they observe each type of band? What was the constituent
isotope that each band contained?
2) Meselson and Stahl’s experiment indicated that DNA replicates semiconservatively.
What percentage of DNA double helixes would contain one of the original parent strands
after four generations of replication?
3) In a conservative model of replication the original double-stranded molecule is
conserved and both strands of the replicated molecule are new. Describe how Meselson
and Stahl’s results would have differed if DNA replicated conservatively.
Answers