# Roles of DNA polymerases delta and epsilon in replication, repair, and genomic fidelity

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $316,000

## Abstract

Abstract
 In eukaryotes, DNA polymerases (Pols)  and  play important roles in replication, but how these Pols
contribute to the replication of the leading DNA strand has remained unclear. While the widely accepted model
posits that Pol replicates the leading strand and Pol replicates the lagging strand, we recently published
evidence that Pol replicates both the leading and lagging DNA strands. Nevertheless, important issues
pertaining to their roles in replication remain to be resolved. Here we propose a number of highly innovative
ideas and experimental approaches to unambiguously establish the roles of Pol and Pol in replication. To
determine whether Pol or Pol replicates the leading strand, in Aim 1 we will analyze Pol-generated errors on
the two DNA strands in genes located at different chromosomal sites and genome-wide in a number of different
yeast strains, and we will also examine whether Pol-generated errors occur on the leading stand; in Aim 2 we
will use mutations in the PCNA binding domain of Pol and Pol to determine whether Pol plays a major role in
replicating both DNA strands or whether Pol replicates the leading strand, and we will carry out studies to
analyze the genetic basis of the mutator phenotype of the pol2M-644G and the exonuclease defective pol2-4
Pol mutant alleles; and in Aim 3, we will determine whether as indicated from our genetic studies, Pol
incorporates rNMPs on the leading strand during its roles in recombination and mismatch repair, and not during
replication. Altogether, we expect that the proposed studies will resolve the outstanding issues relating to the
role of Pols  and  in replication, and they will have important bearing on DNA replication and associated DNA
repair processes and on the understanding of the roles of these Pols in genomic fidelity.

## Key facts

- **NIH application ID:** 10229497
- **Project number:** 5R01GM129689-04
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** SATYA PRAKASH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $316,000
- **Award type:** 5
- **Project period:** 2018-08-07 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229497

## Citation

> US National Institutes of Health, RePORTER application 10229497, Roles of DNA polymerases delta and epsilon in replication, repair, and genomic fidelity (5R01GM129689-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229497. Licensed CC0.

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