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Robertson describes a partner activity and then a whole-class activity that use modeling to teach DNA replication, connect it to the shape of chromosomes during mitosis, and help students understand how daughter cells have the same DNA. Modeling is integral to science, helping students understand phenomena that may not be seen. Yes, students might extract DNA in a lab activity, but they cannot zoom in to the molecular level to directly observe it.
Ask your students what a chromosome looks like and they will probably describe an X-shaped object similar to what is shown in Figure 1 (page 48). But how much do they really know about chromosomes?
?¢ Do your students know that the X-shaped chromosomes result from DNA replication?
?¢ Can they make a connection between chromosomes during mitosis and DNA replication?
?¢ Do they realize that chromosomes are only in that replicated form if the cell is preparing for and then going through cell division and that during the majority of a cell's life cycle the chromosomes are not shaped like an X?
This article describes a partner activity and then a whole-class activity that use modeling to teach DNA replication, connect it to the shape of chromosomes during mitosis, and help students understand how daughter cells have the same DNA.
Modeling is integral to science, helping students understand phenomena that may not be seen. Yes, students might extract DNA in a lab activity, but they cannot zoom in to the molecular level to directly observe it.
Before engaging students in this activity about DNA replication, I incorporate lessons about DNA structure using online resources, handouts, body modeling, and chenille stem modeling (Robertson 2016b). I also have students create paper chromosomes (Robertson 2016a) to familiarize them with the terms genome, chromosome, gene, gene locus, and allele. (You need at least one of the paper chromosome models for the whole-class activity described later.)
DNA replication
DNA replication is complicated, involving several different enzymes. Before replication, the cell accumulates DNA nucleotides (the building blocks of DNA) used in the process. These nucleotides are readied for replication by the addition of phosphate groups and are then referred to as deoxyribonucleoside 5´-triphosphates (dNTPs). Most of the early research on DNA replication was done with E. coli, but replication in eukaryotes is now also well known (Cooper 2000). History of the research and explanation of DNA replication is available online (see "On the web").
Simply put, DNA replication is semi-conservative, meaning that the double helix is essentially split in half by breaking apart the hydrogen bonds that hold together the base pairs of each step. Since the base pairs combine only in certain ways (adenine with thymine, and guanine with cytosine), rebuilding the missing half of each half-strand results in two identical strands of DNA.
However, the details of what is involved in DNA replication can be complicated. For instance, as many as 11 different DNA polymerases (DNAP) are found in eukaryotic cells (Campbell et al. 2008). In addition, DNAP molecules can only synthesize DNA in a 5-prime to 3-prime (5´ to 3´) direction (but only after building offa primer of RNA). This means that the two halves of the DNA are being replicated in opposite directions, resulting in what are referred to as lagging and leading strands. Also, replication does not start at one end of a chromosome and move all the way to the other end; several replication forks form along the entire length.
Because DNA replication can be taught at various levels of detail, you should differentiate your instruction based on the level of the student or class. For the partner and whole-class activities described here, I give introductory detail equivalent to what I taught sophomore general biology students. The idea is to keep it simple but still provide a model to help students understand the big-picture concept of semi-conservative replication and connect it to the shape of a duplicated chromosome.
Safety note: Remind students to handle scissors safely and to keep their own and their classmate's fingers/hands/arms clear while cutting. Be aware of any students with motor skill difficulties and take necessary safety precautions with all students.
Partner activity
Student partners should sit side by side for this 15-minute activity. Partners need a total of two markers or pencils that are different colors, a pair of scissors, and a 4.25 × 11 in. piece of paper (I prepared these in advance by cutting 8.5 × 11 in. sheets in half vertically). The paper should be positioned flat on the desk between the partners so that the short sides are at the top and bottom.
To start, I ask the student on the leftto use one colored marker to write 12-15 capital letters for the DNA bases (A, T, G, or C) down the leftedge of the paper. Then, I have the partner seated on the right use the same colored marker/pencil and write the complementary bases along the right edge of the paper (Figure 2). (Note: These instructions refer to the students' perspective of leftand right.) I remind students that we are not showing the phosphate groups and deoxyribose sugar molecules that make up the sides of DNA, even though they are important to the overall structure.
Now I have partners cut their 4.25 × 11" paper strip vertically through the middle. I ask the leftpartner to take the lefthalf of the cut strip. Using the second colored marker/ pencil (a different color than the first) and writing along the newly cut edge, this student should write the letters representing complementary bases (A, T, G, or C). Afterward, the leftpartner hands the second colored marker to the right partner. That partner takes the right half of the cut strip and writes the letters for complementary bases along the newly cut leftedge (Figure 3).
To finish, I have each partner take one of the two strips and read out loud their base pair sequences from top to bottom to compare. Partners realize that the two new pieces of DNA are identical to each other. I also have students examine the original DNA sequence (in the first color used) and compare it to each of the two new pieces of DNA. Students discover that the original strand is identical to each of the two new strands. This is a good time to challenge students to think about why this happens and to allow discussion between partners. Confirm with students that the complementarity of the DNA base pairs ensures the creation of two pieces of identical DNA.
Figure 3 shows the result of this part of the activity. Because of the complementarity of DNA base pairs and the use of two different colors, students now have a visual representation of semiconservative DNA replication. Before moving on, I ask students why a cell would make an exact copy of its DNA. (Answer: The cell is going to divide, and each new cell needs a complete set of chromosomes.) I explain that this type of replication is referred to as "semi-conservative" because one side of each new piece of DNA is original (or conserved) while the other consists of new nucleotides. I also point out that it was easy for us to model semiconservative DNA replication for this very short piece of DNA, but then I ask them to think about trying to model the replication of 46 chromosomes with a total of three billion base pairs in one hour (NHGRI 2010).
An important aspect of modeling is to evaluate the accuracy of the model, so I always take time in class to do this. I ask students if they think the DNA molecule reduces in width by one-half each time replication takes place (as the cut paper model does). "No!" they reply. I then ask how we could revise this activity to more accurately reflect that the overall width of a DNA molecule does not change from before to after replication. Essentially, we would need to add a new strip of 2.125 × 11 in. paper after cutting the DNA open to represent the width of the new nucleotides. However, this would become unwieldy during the simple partner demonstration of DNA replication. I believe it is better to cut, replicate, and afterward point out this shortcoming of the model. You may also ask students if they think replication happens error-free. Replication has an estimated error rate of one in 100,000 nucleotides, but DNA repair mechanisms reduce that to an estimated 1 in 10 billion nucleotides (Campbell et al. 2008).
Students now understand the concept of semi-conservative replication and are ready to discover details in the steps involved (see "On the web"). How deep to go is the teacher's choice, depending on district curriculum and prerequisites for your school's upper-level courses. This article does not address all depths of DNA replication but I will add greater detail in the whole-class activity, which is next.
Whole-class activity
For this activity, we use at least one of the paper chromosomes consisting of DNA base pairs written on 10-15 of the 4.25 × 11" sheets with short ends taped together to create one long piece (see instructions in the "Modeling Chromosomes" whole class activity [Robertson 2016a]). For my students, the whole class activity for DNA replication takes about 20-30 minutes. To have maximum student participation in a class of 24, I would use two different paper chromosomes with 10-14 students at each one, depending on the length of it.
For replication of one paper chromosome, I give four or more students the role of helicase, the enzyme that untwists the double helix and breaks apart the hydrogen bonds that hold complementary base pairs together. I have these students get scissors for cutting paper and then instruct them to stand along the paper chromosome with one student at each end and the rest spread out along the length (remind students to use scissors safely). Depending on the length of your paper chromosome, you may adjust the number of students representing helicase so there are enough to stand about 1-2 m from each other along the strip.
I use several students for the job of DNAP (DNAP III in particular; I do not include other DNAP molecules in this activity) and have them assemble near the helicase students. I recommend having 2-4 DNAP students by each helicase student. These DNAP students have writing utensils and, once the heli- case cuts the hydrogen bonds and splits the paper chromosome lengthwise, begin writing complementary base pairs along the cut edges just as they did in the partner activity.
A few notes about detail before continuing:
?¢ For sophomore general biology classes, I do not worry about the 5´ to 3´ working direction of DNAP on the newly copied side of the DNA (3´ to 5´ from the perspective of the original DNA).
?¢ However, for sophomore honors and upper level classes I want to establish the 5´ and 3´ ends of the paper chromosome before starting and then have students only write new bases on the cut edges in a 5´ to 3´ direction for the new strands.
?¢ For this whole-class activity, I do not include detail on the work of primase to create RNA primers, but you could include that information by adding students to act as primase.
?¢ Finally, I have found the use of paper chromosome models very useful in helping upper-level students visualize lagging and leading strands. Students use the model to collaborate and determine which newly replicated side would be lagging strands and which would be leading strands at various replication forks along the length of the chromosome.
After all students are in place, I ask them to begin. Students playing the role of helicase cut open the chromosome along its length (Figure 4, p. 50) while students playing the role of DNAP write new bases on the cut edges (Figure 5, p. 50).
As students work, I challenge them with information about the rate of DNAP in replication (Example: "The real DNAP works as fast as 50 nucleotides added per second in human cells [Campbell et al. 2008].... See if you can go faster!!"). I watch carefully for the middle section to be finished and then use a piece of masking tape to reconnect the two pieces at one spot as the students continue working. This taped spot represents the centromere (Figure 6, p. 51).
In my classes, we typically cover DNA structure after cell division (both mitosis and meiosis) and genetics. Now is the perfect time for me to remind students what they learned in cell division. Once students have finished replication, I hold the duplicated paper chromosome model at the taped centromere and have a few volunteer students hold the four ends of the duplicated chromosome. I ask the class:
?¢ "What does this remind you of from previous chapters?" Answer: This X-shaped paper model represents a duplicated chromosome.
?¢ I dig a little deeper by asking: "What does each strip of DNA represent?" Answer: Sister chromatids.
?¢ I also ask: "What is represented by the place where I taped the sister chromatids together?" Answer: The centromere.
?¢ "How do the two sister chromatids compare to each other?" Answer: They are identical (barring any replication mistakes).
To quickly reenact mitosis, I have the students holding the paper model move to the middle of the room. After I remind students of metaphase and the duplicated chromosomes lining up at the equator, I ask them what happens next. When students recall how the sister chromatids are separated in anaphase, we reenact this with the paper model.
I enlist two additional student helpers to act as spindle fibers and hold the model at the taped point (the centromere). After I tear the masking tape, these students pull away the two pieces as the other students holding the ends let go. We then discuss telophase and how the cell will split into two new cells. I make sure to ask students how the DNA in those two cells compares (they are identical!). I also remind students that DNA replication only occurs if the cell is going to divide.
Now we have come full circle in modeling DNA replication and connecting it to the shape of a duplicated chromosome. It is helpful to have students view a video of cell division (see "On the web") to make the connection between those events and what we modeled at the end of our whole-class activity.
Conclusion
By using models, students increase their comprehension and understanding of science in a way that is difficult to accomplish with lectures alone. I think you will find the partner and whole-class modeling activities described here beneficial in helping your students better understand DNA replication, how it relates to chromosome appearance during cell division, and how it ensures the continuity of genetic information from one generation of cells to the next.
ON THE WEB
Cells can replicate their DNA precisely: www.nature.com/scitable/topicpage/ cells-can-replicate-their-dna-precisely-6524830
DNA replication (basic detail): www.hhmi.org/biointeractive/dna-replicationbasic- detail
DNA replication (schematic): www.hhmi.org/biointeractive/dna-replication-schematic
Mitosis video (note: sister chromatids appear close together until anaphase): www.youtube.com/watch?v=L61Gp_d7evo
What is DNA replication? www.yourgenome.org/facts/what-is-dna-replication
REFERENCES
Campbell, N.A., J.B. Reece, L.A. Urry, M.L. Cain, S.A. Wasserman, P.V. Minorsky, and R.B. Jackson. 2008. AP Edition Biology. New York: Benjamin/Cummins.
Cooper, G.M. 2000. The cell: A molecular approach. 2nd edition. Sunderland, MA: Sinauer Associates.
National Governors Association Center for Best Practices and Council of Chief State School Officers (NGAC and CCSO). 2010. Common core state standards. Washington, DC: NGAC and CCSO.
National Human Genome Research Institute (NHGRI). 2010. Chat Q&A: How long does it take to replicate one DNA strand? www.genome.gov/dnaday/q. cfm?aid=1284&year=2010
NGSS Lead States. 2013. Next generation science standards: For states, by states. Washington, DC: National Academies Press. www.nextgenscience.org.
Robertson, C. 2016a. Modeling chromosomes. The Science Teacher 83 (9): 45-50.
Robertson, C. 2016b. Modeling DNA. The Science Teacher 83 (5): 26-32.
Copyright National Science Teachers Association Feb 2018