What enzyme performs proofreading in human base excision repair? Outline the evidence supporting

step 1 Assertion DNA polymerase 1 acts as proofreader. Reason DNA polymerase 1 removes mismatched nucle

What enzyme performs proofreading in human base excision...

Key Concepts

3?–5? Exonuclease Proofreading Activity

Proofreading is a function provided by certain DNA polymerases that use a 3?–5? exonuclease activity to remove incorrectly incorporated nucleotides immediately after their addition. This activity increases the overall fidelity of DNA synthesis by ensuring that only the correct nucleotides remain in the DNA strand, an important feature during both replication and repair processes.

DNA Polymerase Delta

DNA polymerase delta is one of the major replicative polymerases in eukaryotic cells and is known for its intrinsic 3?–5? exonuclease proofreading activity. In the context of BER, particularly in long?patch repair where the repair patch extends beyond a single nucleotide, evidence from in vitro repair assays and mutagenesis studies indicates that polymerase delta can carry out the necessary DNA synthesis while also proofreading to correct errors. This dual function helps maintain genetic fidelity during the repair process, distinguishing it from polymerases like Pol ? that lack such proofreading capabilities.

Base Excision Repair

Base excision repair (BER) is a cellular mechanism responsible for identifying and correcting small base lesions that result from oxidation, alkylation, deamination, or spontaneous loss of a base. The process involves multiple steps—including lesion recognition by a glycosylase, incision of the DNA backbone by an AP endonuclease, gap filling by a DNA polymerase, and sealing by a DNA ligase—to restore the correct nucleotide sequence and maintain genomic integrity.

DNA Polymerase Role and Fidelity in BER

DNA polymerases are central to the repair synthesis step in BER. While the short?patch pathway typically uses DNA polymerase beta (Pol ?) for gap filling, Pol ? is characterized by its lack of 3?–5? exonuclease proofreading activity. Consequently, in repair scenarios where fidelity is especially critical or when longer patches are synthesized, additional mechanisms are required to correct any misincorporated nucleotides.

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