What is the Difference Between DNA Ligase and DNA Polymerase

The main difference between DNA ligase and DNA polymerase is that DNA ligase joins single-stranded breaks in double-stranded DNA during DNA replication, repair, and recombination whereas DNA polymerase adds complementary DNA nucleotides to a growing strand in the 5′ to 3′ direction during DNA replication. Furthermore, DNA ligase plays a critical role in maintaining genome integrity while DNA polymerase is important for the synthesis of new DNA required by cell division. 

DNA ligase and DNA polymerase are two enzymes which play an important role in DNA replication and repair. Significantly, they catalyze the formation of phosphodiester bonds. 

Key Areas Covered 

1. What is DNA Ligase
     – Definition, Features, Importance
2. What is DNA Polymerase
     – Definition, Features, Importance
3. What are the Similarities Between DNA Ligase and DNA Polymerase
     – Outline of Common Features
4. What is the Difference Between DNA Ligase and DNA Polymerase
     – Comparison of Key Differences

Key Terms 

DNA Ligase, DNA Polymerase, DNA Repair, DNA Replication

What is DNA Ligase 

DNA ligase is the enzyme that plays an essential role in joining mainly single-strand breaks in the double-stranded DNA during DNA replication, repair, and recombination. It works in an ATP-dependent manner. Generally, there are four types of DNA ligases in mammals. They are DNA ligase I, II, III, and IV. Here, DNA ligase I is the enzyme responsible for ligating the nascent DNA of the lagging strand after the removal of RNA primers from the Okazaki fragments during DNA replication. Basically, it is a monomer of 102 kDa with two clearly distinct regions: 78 kDa C-terminal domain containing the active site and 24 kDa N-terminal containing nuclear localization signal, directing the enzyme to the region of DNA replication.

Figure 1: DNA Ligase Function

Furthermore, DNA ligase II is responsible for DNA repair. But, this enzyme does not contain a gene, and it is formed by alternative splicing of the gene product of DNA ligase III gene. Moreover, DNA ligase III is responsible for the ligation of DNA during nucleotide excision repair and in recombinant fragments. On the other hand, DNA ligase IV ligates double-strand break during non-homologous end-joining pathway. The other two common types of DNA ligases include E. coli DNA ligase and T4 ligase.  

What is DNA Polymerase 

DNA polymerase is the critical enzyme responsible for adding complementary nucleotides to the growing strands of DNA during DNA replication. Moreover, it proceeds in the 5′ to 3′ direction on the growing strand. It requires an RNA primer, in other words, a pre-existing 3′-OH group for the initiation of synthesis during DNA replication. Generally, the six types of DNA polymerases in eukaryotes are DNA polymerase α, β, γ, δ, ε, and ζ. However, only three of them take part in DNA replication. They are DNA polymerase α, δ, and ε. Basically, other DNA polymerases take part in DNA repair.

Figure 2: DNA Polymerase Function

Moreover, the main types of DNA polymerases that occur in prokaryotes include DNA polymerase I, I, III, IV, and V. Here, DNA polymerase I has both 3′ to 5′ and 5′ to 3′ exonuclease activity. Additionally, DNA polymerase II only has 3′ to 5′ exonuclease activity. Meanwhile, DNA polymerase III holoenzyme is the main enzyme responsible for DNA replication in prokaryotes. On the contrary, DNA polymerase IV takes part in non-targeted mutagenesis. DNA polymerase V takes part in DNA repair. 

Similarities Between DNA Ligase and DNA Polymerase 

• DNA ligase and DNA polymerase are two enzymes whose substrate is double-stranded DNA. 
• They catalyze the formation of phosphodiester bonds.  
• Both enzymes play an important role in DNA replication and repair. 
• Moreover, multiple types of these enzymes occur in organisms with slightly different functions. 
• They are important for genetic engineering techniques including DNA cloning, DNA sequencing, DNA labeling, mutagenesis, and other in vitro DNA manipulations. 

Difference Between DNA Ligase and DNA Polymerase 

Definition 

DNA ligase refers to a specific type of enzyme, which facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond while DNA polymerase refers to an enzyme, which synthesizes DNA molecules from deoxyribonucleotides, the building blocks of DNA.   

Types 

The types of DNA ligases include DNA ligase I, II, III, IV, E. coli DNA ligase, and T4 ligase while the types of DNA polymerases include DNA polymerase α, β, γ, δ, ε, and ζ in eukaryotes and DNA polymerase I, I, III, IV, and V in prokaryotes.  

Function 

DNA ligase joins single-stranded breaks in double-stranded DNA during DNA replication, repair, and recombination while DNA polymerase adds complementary DNA nucleotides to a growing strand in the 5′ to 3′ direction during DNA replication. 

Activated Intermediate and Leaving Group 

The activated intermediate of DNA ligase is a DNA-adenylate and AMP is the leaving group while the activated intermediates of DNA polymerase are deoxyribonucleoside triphosphates and leaving groups are pyrophosphates. 

Significance 

Moreover, DNA ligase works in an ATP-dependent manner, while DNA polymerase adds nucleotides in the 5′ to 3′ direction to the growing strand. 

Importance 

While DNA ligase plays a critical role in maintaining genome integrity, DNA polymerase is important for the synthesis of new DNA required by cell division. 

Conclusion 

DNA ligase is the enzyme responsible for the ligation of single-strand breaks in double-stranded DNA. Generally, it is important in DNA replication, repair, and genetic recombination. On the other hand, DNA polymerase is the main enzyme responsible for the addition of complementary bases to the growing DNA strand during DNA replication. Furthermore, it is important for the synthesis of missing bases during DNA repair. Therefore, both enzymes are important for the maintenance of the integrity of DNA. However, the main difference between DNA ligase and DNA polymerase is their function.   

References:

1. Mossi, Romina, et al. “DNA Ligase I Selectively Affects DNA Synthesis by DNA Polymerases δ and ε Suggesting Differential Functions in DNA Replication and Repair.” Journal of Biological Chemistry, vol. 273, no. 23, 1998, pp. 14322–14330., doi:10.1074/jbc.273.23.14322.

Image Courtesy:

1. “Heather Tsai DNA Ligase” By HeatherTsai – Own work (CC BY-SA 3.0) via Commons Wikimedia   
2. “DNA replication en” By LadyofHats Mariana Ruiz – Own work Image renamed from File:DNA replication.svg (Public Domain) via Commons Wikimedia   

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