An enzyme, DNA polymerase, catalyzes the synthesis of new DNA molecules from deoxyribonucleotides (the building blocks of DNA). It is crucial in living organisms’ DNA replication, repair, and recombination processes.
DNA polymerases attach new nucleotides to the 3′ end of a growing DNA strand by forming phosphodiester bonds between the new nucleotide and the existing DNA strand. This process ensures accurate copying of the genetic information stored in DNA during cell division and other cellular activities.
DNA polymerases also possess proofreading capabilities to correct errors that may occur during DNA synthesis, contributing to the overall allegiance of DNA replication and maintenance of genetic integrity.
Table of Contents
Structure of DNA Polymerase
DNA polymerases have a complex structure, allowing them to carry out their DNA replication and repair functions. The structure of DNA polymerase can vary slightly among different organisms and types of polymerases, but they generally share standard features.
- Catalytic Core: DNA polymerase’s catalytic core contains the active site responsible for catalyzing the polymerization reaction. It includes domains involved in binding DNA and nucleotides and catalyzing the formation of phosphodiester bonds between nucleotides.
- Thumb Domain: This domain is involved in DNA binding and helps stabilize the interaction between DNA polymerase and the DNA template strand. It is called the “thumb” domain because of its structural resemblance to a thumb in some DNA polymerase structures.
- Palm Domain: The palm domain contains the active site of the polymerase enzyme, where nucleotide polymerization occurs. It also houses the catalytic residues, which are necessary to catalyze the addition of nucleotides to the growing DNA strand.
- Fingers Domain: The fingers domain is involved in the movement of the DNA and nucleotide substrates during the polymerization process. It undergoes conformational changes to allow the binding of incoming nucleotides and their incorporation into the growing DNA chain.
- Exonuclease Domain (Proofreading): Some DNA polymerases have an exonuclease domain responsible for proofreading the newly synthesized DNA strand. This domain can remove incorrectly incorporated nucleotides by excising them from the 3′ end of the growing DNA chain, improving the overall fidelity of DNA replication.
- Accessory Proteins: Besides the core catalytic domains, DNA polymerases often interact with accessory proteins that assist in various aspects of DNA replication, such as processivity, primer recognition, and coordination with other replication machinery components.
Overall, the structure of this is highly specialized to perform its essential functions in DNA replication and repair accurately and efficiently. Variations in structure and function exist among different DNA polymerase types, reflecting their diverse roles in maintaining genomic integrity across different organisms.
Types of DNA Polymerase
There are several types of polymerases involved in various DNA-related processes, including DNA replication, repair, and synthesis. The types of DNA polymerase vary among prokaryotes and Eukaryotes.
Types of DNA Polymerase Found in Prokaryotes
Prokaryotic organisms, such as bacteria, have several DNA polymerases that play different roles in DNA replication, repair, and other cellular processes.
- DNA Polymerase I (Pol I):
- Functions in DNA repair and gap filling during DNA synthesis.
- It has 5′ to 3′ polymerase activity for DNA synthesis.
- This type also possesses a 3′ to 5′ exonuclease (proofreading) activity, which helps correct errors during replication.
- It also assists in removing RNA primers during Okazaki fragment maturation in DNA replication.
- DNA Polymerase II (Pol II):
- She is involved in DNA repair processes, especially those that respond to DNA damage caused by environmental factors such as UV light.
- It exhibits 5′ to 3′ polymerase activity and lacks 3′ to 5′ exonuclease activity.
- DNA Polymerase III (Pol III):
- It is prokaryotes’ primary DNA replication enzyme, including bacteria like Escherichia coli (E. coli).
- The highly processive enzyme is responsible for producing the leading as well as lagging strands during DNA replication.
- They comprises of multiple subunits, including the core catalytic subunit responsible for DNA synthesis (Pol III core).
- DNA Polymerase IV (Pol IV) and DNA Polymerase V (Pol V):
- These are specialized DNA polymerases involved in translesion DNA synthesis, particularly when regular DNA polymerases encounter DNA lesions or damage.
- Pol IV and Pol V are error-prone and can replicate past damaged sites with reduced fidelity, allowing cells to tolerate DNA damage temporarily.
- DNA Polymerase VI (Pol VI):
- Found in certain bacterial species.
- Functions in translesion DNA synthesis and can bypass DNA lesions, similar to Pol IV and Pol V.
These DNA polymerases in prokaryotes work together in a coordinated manner during DNA replication, repair, and other DNA-related processes to ensure accurate DNA synthesis, maintain genomic stability, and respond to DNA damage. Each type has specific functions and characteristics that contribute to the fidelity and efficiency of DNA replication and repair in prokaryotic cells.
Types of DNA Polymerase Found in Eukaryotes
Eukaryotic organisms, like plants, animals, fungi, and protists, possess a variety of DNA polymerases that are required in different aspects of DNA replication, repair, and maintenance.
- DNA Polymerase α (Pol α):
- Involved in the initiation of DNA replication.
- Synthesizes RNA-DNA primers on both leading and lagging strands during replication initiation.
- Works in conjunction with other replication proteins to form the pre-replication complex.
- DNA Polymerase δ (Pol δ):
- The main DNA replication enzyme is for the lagging strand during DNA replication.
- It exhibits high processivity and fidelity.
- Involved in synthesizing Okazaki fragments on the lagging strand.
- DNA Polymerase ε (Pol ε):
- The main DNA replication enzyme is the leading strand during DNA replication.
- Highly processive and accurate.
- Works in coordination with other replication proteins to synthesize the leading strand continuously.
- DNA Polymerase β (Pol β):
- Involved in base excision repair (BER) pathway.
- This polymerase specializes in filling the gaps after damaged bases are removed during BER.
- DNA Polymerase γ (Pol γ):
- It is present in mitochondria (mitochondrial DNA polymerase).
- Responsible for replicating and maintaining the mitochondrial genome.
- This type of polymerase plays a crucial role in mitochondrial DNA repair processes.
- DNA Polymerase η (Pol η):
- Involved in translesion synthesis (TLS).
- During DNA replication, specialized in bypassing UV-induced DNA lesions, such as thymine dimers.
- DNA Polymerase κ (Pol κ):
- Involved in translesion synthesis (TLS).
- Specialized in bypassing bulky DNA lesions, such as those caused by certain chemical agents.
- DNA Polymerase ι (Pol ι):
- Involved in translesion synthesis (TLS).
- Specialized in bypassing certain DNA lesions and insertions/deletions during DNA replication.
- DNA Polymerase ζ (Pol ζ):
- Involved in translesion synthesis (TLS) and DNA damage tolerance.
- Can replicate past DNA lesions with low fidelity, leading to mutagenesis under certain conditions.
- DNA Polymerase Rev1 (Pol Rev1):
- Involved in translesion synthesis (TLS) and DNA damage tolerance.
- It plays a role in generating mutagenic DNA synthesis during TLS.
These eukaryotic DNA polymerases have diverse functions and specialize in DNA replication and repair pathways. They contribute to maintaining genomic stability, accurately replicating DNA, and repairing damaged DNA to ensure the integrity of the genetic information in eukaryotic cells.
Functions
DNA polymerase’s primary function is to act as a catalyst during the synthesis of new DNA strands by adding new nucleotides to the growing DNA chain during DNA replication, repair, and recombination processes.
- DNA Replication: This enzyme plays a central role in DNA replication, where it copies the entire genome of a cell before cell division. During replication, DNA polymerase synthesizes new DNA strands complementary to the template strands. The leading strand synthesizes continuously in the 5′ to 3′ direction. However, the lagging strand synthesizes discontinuously in Okazaki fragments.
- Nucleotide Addition: It catalyzes the addition of deoxyribonucleotides (dNTPs) to the 3′ end of the growing DNA strand. It forms phosphodiester bonds between the incoming nucleotide and the last nucleotide of the ever-increasing strand, extending the DNA chain.
- Proofreading: Many DNA polymerases possess proofreading capabilities to maintain high fidelity during DNA synthesis. They have 3′ to 5′ exonuclease activity, allowing them to find and correct errors made during replication by removing incorrectly incorporated nucleotides from the 3′ end of the growing strand.
- Processivity: DNA polymerases are highly processive enzymes that can add multiple nucleotides sequentially without dissociating from the DNA template. This processivity ensures efficient DNA synthesis during replication and repair processes.
- DNA Repair: In addition to replication, DNA polymerases assist in DNA repair mechanisms. For example, during base excision repair, specialized DNA polymerases help fill the gaps left after the removal of damaged bases. Similarly, DNA polymerases are involved in nucleotide excision repair and mismatch repair pathways to correct various types of DNA damage and mismatches.
- Translesion Synthesis: Some DNA polymerases are specialized in bypassing DNA lesions or damage during replication. These polymerases, known as translesion polymerases, can replicate past damaged sites in the DNA template, albeit with reduced fidelity, to prevent replication stalling and maintain genome integrity.
References
- Nasheuer, Heinz & H.-P, & Pospiech, Helmut & Syvaoja, Juhani. (2006). DNA Polymerases..
- Steitz, T. A. (1999). DNA polymerases: Structural diversity and common mechanisms. Journal of Biological Chemistry, 274(25), 17395–17398. https://doi.org/10.1074/jbc.274.25.17395
- Pospiech, H. and Syväoja, J.E. (2003) DNA Polymerase ε – More Than a Polymerase. TheScientificWorldJOURNAL 3, 87– 104.
