Theme 6: What Causes Cancer?

6.3 DNA Replication and Repair Mechanisms

Learning Objectives

By the end of this section, you will be able to:

  • Explain the process of DNA replication
  • Differentiate between mismatch repair and nucelotide excision repair
  • Explain the role of ultraviolet light in causing DNA mutations


When a cell divides, it is important that each daughter cell receives an identical copy of the DNA. This is accomplished by the process of DNA replication. The replication of DNA occurs during the synthesis phase, or S phase, of the cell cycle, before the cell enters mitosis or meiosis.

The elucidation of the structure of the double helix provided a hint as to how DNA is copied. Recall that adenine nucleotides pair with thymine nucleotides, and cytosine with guanine. This means that the two strands are complementary to each other. For example, a strand of DNA with a nucleotide sequence of AGTCATGA will have a complementary strand with the sequence TCAGTACT (Figure 1).


Figure shows the ladder-like structure of DNA, with complementary bases making up the rungs of the ladder.
Figure 1. The two strands of DNA are complementary, meaning the sequence of bases in one strand can be used to create the correct sequence of bases in the other strand. 


Because of the complementarity of the two strands, having one strand means that it is possible to recreate the other strand. This model for replication suggests that the two strands of the double helix separate during replication, and each strand serves as a template from which the new complementary strand is copied (Figure 2).


Illustration shows the semiconservative model of DNA synthesis. In the semi-conservative model, each newly synthesized strand pairs with a parent strand.
Figure 2. The semiconservative model of DNA replication is shown. Gray indicates the original DNA strands, and blue indicates newly synthesized DNA.


During DNA replication, each of the two strands that make up the double helix serves as a template from which new strands are copied. The new strand will be complementary to the parental or “old” strand. Each new double strand consists of one parental strand and one new daughter strand. This is known as semiconservative replication. When two DNA copies are formed, they have an identical sequence of nucleotide bases and are divided equally into two daughter cells.


DNA Replication in Eukaryotes

The process of DNA replication can be summarized as follows:

  1. DNA unwinds at the origin of replication.
  2. New bases are added to the complementary parental strands. The matching of free nucleotides to the parental strands is accomplished by an enzyme called DNA polymerase.
  3. Primers are removed, new DNA nucleotides are put in place of the primers and the backbone is sealed by DNA ligase.


DNA Repair

DNA polymerase can make mistakes while adding nucleotides. It edits the DNA by proofreading every newly added base. Incorrect bases are removed and replaced by the correct base, and then polymerization continues (Figure 3a). Most mistakes are corrected during replication, although when this does not happen, the mismatch repair mechanism is employed. Mismatch repair enzymes recognize the wrongly incorporated base and excise it from the DNA, replacing it with the correct base (Figure 3b). In yet another type of repair, nucleotide excision repair, the DNA double strand is unwound and separated, the incorrect bases are removed along with a few bases on the 5′ and 3′ end, and these are replaced by copying the template with the help of DNA polymerase (Figure 3c). Nucleotide excision repair is particularly important in correcting thymine dimers, which are primarily caused by ultraviolet light. In a thymine dimer, two thymine nucleotides adjacent to each other on one strand are covalently bonded to each other rather than their complementary bases. If the dimer is not removed and repaired it will lead to a mutation. Individuals with flaws in their nucleotide excision repair genes show extreme sensitivity to sunlight and develop skin cancers early in life.


Part a shows DNA polymerase replicating a strand of DNA. The enzyme has accidentally inserted G opposite A, resulting in a bulge. The enzyme backs up to fix the error. In part b, the top illustration shows a replicated DNA strand with a G–T base mismatch. The bottom illustration shows the repaired DNA, which has the correct G–C base pairing. Part c shows a DNA strand in which a thymine dimer has formed. An excision repair enzyme cuts out the section of DNA that contains the dimer so that it can be replaced with a normal base pair.
Figure 3. Proofreading by DNA polymerase (a) corrects errors during replication. In mismatch repair (b), the incorrectly added base is detected after replication. The mismatch repair proteins detect this base and remove it from the newly synthesized strand by nuclease action. The gap is now filled with the correctly paired base. Nucleotide excision (c) repairs thymine dimers. When exposed to UV, thymines lying adjacent to each other can form thymine dimers. In normal cells, they are excised and replaced.


Most mistakes are corrected; if they are not, they may result in a mutation—defined as a permanent change in the DNA sequence. Mutations in repair genes may lead to serious consequences like cancer.


Section Summary

DNA replicates by a semi-conservative method in which each of the two parental DNA strands act as a template for new DNA to be synthesized. After replication, each DNA has one parental or “old” strand, and one daughter or “new” strand. Errors made during replication are typically repaired. If they are not, mutations can result.


You isolate a cell strain in which the joining together of Okazaki fragments is impaired and suspect that a mutation has occurred in an enzyme found at the replication fork. Which enzyme is most likely to be mutated?Ligase, as this enzyme joins together Okazaki fragments



DNA ligase
the enzyme that catalyzes the joining of DNA fragments together
DNA polymerase
an enzyme that synthesizes a new strand of DNA complementary to a template strand
an enzyme that helps to open up the DNA helix during DNA replication by breaking the hydrogen bonds
mismatch repair
a form of DNA repair in which non-complementary nucleotides are recognized, excised, and replaced with correct nucleotides
a permanent variation in the nucleotide sequence of a genome
nucleotide excision repair
a form of DNA repair in which the DNA molecule is unwound and separated in the region of the nucleotide damage, the damaged nucleotides are removed and replaced with new nucleotides using the complementary strand, and the DNA strand is resealed and allowed to rejoin its complement
a short stretch of RNA nucleotides that is required to initiate replication and allow DNA polymerase to bind and begin replication
replication fork
the Y-shaped structure formed during the initiation of replication
semiconservative replication
the method used to replicate DNA in which the double-stranded molecule is separated and each strand acts as a template for a new strand to be synthesized, so the resulting DNA molecules are composed of one new strand of nucleotides and one old strand of nucleotides
an enzyme that contains a catalytic part and an inbuilt RNA template; it functions to maintain telomeres at chromosome ends
the DNA at the end of linear chromosomes


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Human Biology by Sarah Malmquist and Kristina Prescott is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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