Introduction

DNA synthesis is a fundamental biological process essential for cell replication and repair. The substrates used by DNA polymerases during DNA synthesis are critical for ensuring accurate and efficient genome replication. Among various nucleotide forms, deoxynucleoside triphosphates (dNTPs) are the true substrates for DNA synthesis. This article explains why dNTPs are required, their biochemical role during polymerization, and clarifies common confusions about nucleotide nomenclature.

What Are Deoxynucleoside Triphosphates (dNTPs)?

Deoxynucleoside triphosphates are molecules composed of three components:

• A nitrogenous base (adenine, thymine, cytosine, or guanine)

• A deoxyribose sugar (lacking an -OH group at the 2′ carbon)

• A triphosphate group attached to the 5′ carbon of the sugar

The term “deoxynucleoside triphosphate” emphasizes the sugar-base-phosphate structure, with three phosphate groups providing energy for DNA polymerization.

Why dNTPs Are the Substrates for DNA Synthesis

1. Energy for Polymerization

DNA polymerases catalyze the addition of nucleotides to the growing DNA strand by forming phosphodiester bonds. The reaction involves a nucleophilic attack by the 3′-OH group of the growing strand on the α-phosphate of the incoming dNTP.

• The β and γ phosphates of the dNTP are cleaved off as pyrophosphate (PPi).

• The hydrolysis of pyrophosphate releases energy, driving the polymerization forward.

• This energy release is critical for the formation of the stable phosphodiester bond linking nucleotides.

2. Structural Requirement

• The triphosphate moiety is necessary for recognition and binding by DNA polymerases.

• The deoxyribose sugar (lacking 2′-OH) ensures incorporation into DNA rather than RNA.

• The presence of the base allows correct base pairing with the template strand, ensuring fidelity.

Clarifying Nomenclature: Nucleotide vs. Nucleoside

• A nucleoside consists of a nitrogenous base plus a sugar (no phosphate).

• A nucleotide is a nucleoside with one or more phosphate groups attached.

• The substrate for DNA synthesis is a deoxynucleoside triphosphate (dNTP), which is a nucleotide with three phosphate groups.

• Sometimes “deoxynucleotide triphosphate” is used interchangeably with “deoxynucleoside triphosphate,” but the latter is more precise.

Why Other Molecules Are Not Substrates

• Deoxy Nucleoside Triphosphate (correct substrate): Contains base, sugar, and triphosphate; used by DNA polymerases.

• Deoxy Nucleoside Diphosphate or Monophosphate: Lack the full triphosphate group; insufficient energy for polymerization.

• Ribonucleotide Triphosphate (NTP): Has a ribose sugar with 2′-OH; used in RNA synthesis, not DNA.

• Nucleoside Pyrophosphate: Incorrect term; pyrophosphate is released during polymerization, not a substrate.

Summary Table

Conclusion

The substrate for DNA synthesis is deoxynucleoside triphosphates (dNTPs). These molecules provide both the building blocks and the energy required for DNA polymerases to catalyze the formation of phosphodiester bonds, ensuring faithful replication of the genome. Understanding the structure and function of dNTPs clarifies their central role in DNA replication and repair.

Answer:
The correct substrate for DNA synthesis is (1) Deoxy Nucleotide triphosphate (deoxynucleoside triphosphate).