The importance of DNA replication

DNA is the molecule of heredity and carries the genetic information that specifies the structure and function of organisms. Inherent in its structure is a mechanism for its replication. It is a good example of how structure relates to function. This relationship between DNA structure and function (i.e. copying mechanism) was noted by Watson and Crick, who indicated in their 1953 paper:

“It has not escaped our notice that the specific [base] pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

DNA replication is a complex process and involves more than 20 different proteins, many of which are enzymes. They include Helicase, Primase, DNA Polymerases, DNA Ligase, Topoisomerase, RNase H and the Single-Strand Binding (SSB) Proteins. In organisms such as bacteria, DNA replication usually takes between 40 and 60 minutes. In contrast, human cells take between six and eight hours to replicate all the DNA in their cells (i.e., replicate the genome).

Accuracy of DNA replication

Several mechanisms contribute to the accuracy of DNA replication. They include:

  1. Complementary base pairing: The complementary base pairing between DNA nucleotides eliminates ambiguity during DNA replication. For example, an A (adenosine) in the template strand can only form a base pair with T (thymine) because of the number of hydrogen bonds that form between them. Therefore, A-T is stable, while A-C and A-G are not.

  2. Proofreading: DNA polymerase III can correct errors (misincorporations) during strand elongation. While one part of DNA polymerase incorporates new nucleotides into the elongating strand, another part of the enzyme checks for errors in base pairing. In a DNA molecule that has perfect base pairing between its two strands, the width of the molecule is 2 nm. If the base pairing is incorrect (e.g., A-C or A-G), then the width of the DNA in that region will be greater than 2 nm. The proofreading portion of DNA polymerase can detect such structural deviations and correct those errors.

  3. Mismatch Repair: After replication, specialised proteins scan the new DNA, identify mismatches, remove the incorrect segment, and replace it with the correct nucleotides.

    DNA is the hereditary molecule that carries the genetic information responsible for the structure and function of organisms. Its structure inherently allows for replication, making it a prime example of how structure relates to function. This connection between the structure and function of DNA was highlighted by Watson and Crick in their 1953 paper, where they noted, “It has not escaped our notice that the specific [base] pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

    As a result, the daughter DNA molecules produced after replication are highly accurate copies of the parental DNA. Studies estimate that if DNA polymerase lacked proofreading ability, the error rate would be one incorrect nucleotide per 100,000. However, due to DNA polymerase’s proofreading function, the typical error rate during DNA replication is one incorrect nucleotide per 10 million. When combined with mismatch repair, this error rate decreases to one incorrect nucleotide per 1 billion (Pray, L. (2008). DNA Replication and Causes of Mutation. Nature Education 1(1): 214).