An altered form of a replicative DNA polymerase lacks 3’→ 5’ exonuclease
activity. This alteration would most likely result in which of the following?
A decrease in processivity
An increased mutation rate
An inability to replicate DNA
An inability to remove RNA primers

The altered replicative DNA polymerase lacking 3’→5’ exonuclease activity would most likely cause an increased mutation rate, because 3’→5’ exonuclease is the intrinsic proofreading function that removes misincorporated nucleotides during replication.​

Correct option: Increased mutation rate

Replicative DNA polymerases (like DNA polymerase III in bacteria or Pol δ/Pol ɛ in eukaryotes) possess 5’→3’ polymerase activity to synthesize DNA and a 3’→5’ exonuclease activity to proofread the newly added bases. The 3’→5’ exonuclease removes incorrectly paired nucleotides from the growing 3’ end, thereby increasing fidelity and preventing mutations.​

If this proofreading activity is lost but polymerase activity remains intact, the enzyme can still replicate DNA, but mispaired bases are no longer efficiently removed, leading to a higher error rate and thus an increased mutation rate. Experimental inactivation of 3’→5’ exonuclease in replicative polymerases produces a clear “mutator” phenotype without abolishing synthesis.​

So, the correct answer is: An increased mutation rate.

Why the other options are incorrect

A decrease in processivity

Processivity refers to how many nucleotides a polymerase can add per binding event before dissociating from the template and is mainly determined by interactions with sliding clamp proteins (e.g., β-clamp in bacteria, PCNA in eukaryotes) and the polymerase–DNA interface, not by the proofreading exonuclease activity. Mutations that specifically abolish 3’→5’ exonuclease usually leave processivity largely unchanged, while primarily affecting fidelity (mutation rate). Therefore, loss of 3’→5’ exonuclease is not primarily expected to decrease processivity.​

An inability to replicate DNA

The core catalytic step in chain elongation is the 5’→3’ polymerase activity, which forms phosphodiester bonds by adding deoxyribonucleotides to the 3’-OH of the growing strand. The 3’→5’ exonuclease is a separate active site that proofreads; it is not required for the basic chemistry of nucleotide addition. Experimental systems show that polymerases with disabled 3’→5’ exonuclease still synthesize DNA but do so with reduced fidelity. Hence, replication would still occur, just with more errors, so “an inability to replicate DNA” is incorrect.​

An inability to remove RNA primers

Removal of RNA primers is mediated by 5’→3’ exonuclease (for example, DNA polymerase I in bacteria uses 5’→3’ exonuclease to remove primers while filling gaps with DNA), or by dedicated RNase H and flap endonucleases (such as Fen1) in eukaryotes. The 3’→5’ exonuclease works from the 3’ end and is used for proofreading misincorporated DNA bases, not for removing RNA primers. Therefore, loss of 3’→5’ exonuclease would not prevent primer removal, making this option incorrect.​

Short SEO-style introduction

Loss of 3’→5’ exonuclease activity in a replicative DNA polymerase directly impairs proofreading and raises the mutation rate during DNA replication. While the enzyme can still synthesize DNA via its 5’→3’ polymerase activity, the lack of exonuclease-mediated error correction leads to reduced fidelity without significantly affecting processivity or RNA primer removal. Understanding how loss of 3’→5’ exonuclease activity in DNA polymerase alters replication is essential for exam questions and for interpreting mutator phenotypes in genetics and molecular biology.