43. DNA repair, synthesis and recombination are intimately connected and inter dependent. An apparent commonality between processes of DNA replication

and repair in the enzymatically catalyzed synthesis of DNA polynucleotide segments, which can be assembled with pre-existing polynucleotides, leading to repair or replication. Synthesis of these polynucleotide segments is catalyzed by a group of enzymes DNA-dependantDNA polymerases. In the case of E.coli, DNA polymerase has been isolated in three distinct forms whereas five

main types of polymerase have been isolated from mammalian cells. All the polymerases synthesize polynucleotides only in the 5’à3′ direction. If polynucleotide chains could be elongated in 3’à5′ direction, the hypothetical growing 5′ terminus, rather than the incoming nucleotide, would carry a tri- phosphate that is unsuitable for further elongation. The 3’à5′ exonuclease activity is not associated with all the polymerases and only present in

(A) All E. coli DNA polymerases

(B) Pol l, Pol IV, Pol V, Pol α, Polβ.

(C) Pol l, Pol III, Poi Ꟙ, Poi ϵ

(D) Pol l, Pol IV, POlα, Poi ϵ.

The correct statements are

(1) (A) and (B)        (2) (A), (B) and (C)

(3) (C) only             (4) (A), (C) and (D)

Introduction

DNA polymerases synthesize DNA in the 5′→3′ direction but many also possess a 3′→5′ exonuclease activity that serves as a proofreading function, removing incorrectly incorporated nucleotides to ensure high fidelity during replication. This exonuclease activity is not universal to all polymerases but is present in specific types critical for accurate DNA synthesis.

DNA Polymerases in E. coli

• E. coli has three main DNA polymerases: Pol I, Pol II, and Pol III.

• Pol I: Possesses both 5′→3′ exonuclease (for primer removal) and 3′→5′ exonuclease (proofreading) activities.

• Pol II: Has 3′→5′ exonuclease proofreading activity.

• Pol III: The primary replicative polymerase, also has 3′→5′ exonuclease activity for proofreading.

Thus, all three E. coli DNA polymerases (I, II, III) have 3′→5′ exonuclease activity.

DNA Polymerases in Mammalian Cells

Mammalian cells have at least five main DNA polymerases involved in replication and repair:

• Pol α (alpha): Initiates DNA synthesis; lacks 3′→5′ exonuclease proofreading activity.

• Pol β (beta): Involved in base excision repair; lacks 3′→5′ exonuclease activity.

• Pol γ (gamma): Mitochondrial polymerase; has 3′→5′ exonuclease activity.

• Pol δ (delta): Main lagging strand polymerase; possesses 3′→5′ exonuclease proofreading activity.

• Pol ε (epsilon): Main leading strand polymerase; has 3′→5′ exonuclease proofreading activity.

Evaluating the Given Options

Correct Statements

• (A) All E. coli DNA polymerases have 3′→5′ exonuclease activity

• (C) Pol I, Pol III, Pol γ, Pol ε have 3′→5′ exonuclease activity

Final Answer

(4) (A), (C), and (D) is not fully correct because (D) is false.

(3) (C) only is partly correct but ignores E. coli polymerases.

(2) (A), (B), and (C) is incorrect because (B) is false.

(1) (A) and (B) is incorrect because (B) is false.

The best fit based on the data is:

(4) (A), (C), and (D) — but since (D) is false, the correct choice is:

(3) (C) only

Summary

• All E. coli DNA polymerases (I, II, III) have 3′→5′ exonuclease proofreading activity.

• In mammals, Pol I, Pol III (mitochondrial Pol γ), and Pol ε have 3′→5′ exonuclease activity.

• Pol IV, Pol V (in E. coli), Pol α, and Pol β (in mammals) lack 3′→5′ exonuclease activity.