61. Eukaryotic DNA polymerase a has tightly associated primase activity but moderate processivity. DNA polymerase ϵ and Ꟙ are highly processive but lack primase activity. Given below are four statements about leading and lagging strand synthesis in

eukaryotes. Which one is true?

(1) Both leading and lagging strands are synthesized by DNA polymerase α. Moderate processivity is essential to maintain fidelity of replication.

(2) Entire leading and lagging strands are synthesized by ϵ and Ꟙ. Eukaryotic replication is primer independent process.

(3) Only the lagging strand synthesis needs primer and synthesized by DNA polymerase α.

(4) Primers for both the strands are synthesized by DNA polymerase α followed by “Polymerase switching” with ϵ and Ꟙ

 

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Introduction

Eukaryotic DNA replication involves coordinated activity of multiple DNA polymerases to ensure accurate and efficient genome duplication. DNA polymerase α (Pol α) has primase activity and initiates DNA synthesis by laying down RNA-DNA primers on both strands. The highly processive DNA polymerases ε (Pol ε) and δ (Pol δ) then take over synthesis of the leading and lagging strands, respectively. This process, known as polymerase switching, is essential for replication fork progression.

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Roles of DNA Polymerases in Eukaryotic Replication

• DNA Polymerase α (Pol α):

  • Possesses an associated primase activity.

  • Synthesizes a short RNA primer followed by a short stretch of DNA on both leading and lagging strands.

  • Has moderate processivity and lacks proofreading ability.

• DNA Polymerase ε (Pol ε):

  • Highly processive with proofreading activity.

  • Primarily responsible for continuous synthesis of the leading strand.

• DNA Polymerase δ (Pol δ):

  • Highly processive with proofreading activity.

  • Responsible for discontinuous synthesis of the lagging strand, synthesizing Okazaki fragments.

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Polymerase Switching Mechanism

1. Primer Synthesis:
   Pol α initiates synthesis by creating RNA-DNA primers on both strands.

2. Switching to Processive Polymerases:
   After primer synthesis, Pol α is replaced by Pol ε on the leading strand and Pol δ on the lagging strand.
   This switch allows efficient and high-fidelity DNA synthesis.

3. Lagging Strand Synthesis:
   Pol δ synthesizes Okazaki fragments discontinuously, which are later processed and joined.

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Why Other Options Are Incorrect

• (1) Both strands synthesized by Pol α:
  Incorrect; Pol α only initiates synthesis, not the entire strand.

• (2) Entire strands synthesized by Pol ε and δ, primer independent:
  Incorrect; primer synthesis by Pol α is essential.

• (3) Only lagging strand needs primer and synthesized by Pol α:
  Incorrect; both strands require primers synthesized by Pol α.

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Correct Statement

(4) Primers for both strands are synthesized by DNA polymerase α followed by “polymerase switching” with ε and δ

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Summary Table

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Keywords

eukaryotic DNA replication, DNA polymerase α, DNA polymerase ε, DNA polymerase δ, primase activity, polymerase switching, leading strand synthesis, lagging strand synthesis, Okazaki fragments, replication fork

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Conclusion

In eukaryotic DNA replication, DNA polymerase α synthesizes RNA-DNA primers on both leading and lagging strands. Following this, a critical polymerase switching event occurs where DNA polymerase ε takes over continuous synthesis on the leading strand, and DNA polymerase δ synthesizes the lagging strand discontinuously. This division of labor ensures high fidelity and efficient replication of the eukaryotic genome.

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Correct answer:
(4) Primers for both the strands are synthesized by DNA polymerase α followed by “Polymerase switching” with ε and δ