# Mechanisms of RNA-DNA repair

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $377,348

## Abstract

Polymerase theta (Polq) is a unique polymerase-helicase fusion protein that performs multiple functions in DNA
repair in mammalian cells. Polq was initially characterized as a translesion DNA polymerase due to its ability to
perform replication opposite DNA lesions in vitro, and Polq translesion synthesis (TLS) has now been confirmed
in cells. Our laboratory and others have also identified an essential role for Polq in repairing double-strand breaks
(DSBs) via microhomology-mediated end-joining (MMEJ). Polq has also been implicated in replication repair,
base excision repair, somatic hypermutation and class-switch recombination. Whether this unique and error-
prone polymerase exhibits additional activities in DNA repair remains unknown.
 Here, we discover that recombinant human Polq exhibits robust reverse transcriptase (RT) activity,
whereas all other human DNA polymerases tested from the A, B, Y and X families fail to perform reverse
transcription beyond 1-2 nucleotides. Polq generates identical reverse transcription products as retroviral RTs.
Unexpectedly, Polq exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on
RNA versus DNA templates. These preliminary studies identify Polq as a novel RT in mammalian cells. We plan
to elucidate the molecular basis of Polq RT activity in vitro and investigate multiple RNA-templated DNA repair
(RNA-DNA repair) mechanisms in cells and in vivo by developing the following Aims: 1. To characterize Polq
reverse transcriptase activity in vitro; 2. To elucidate the molecular basis of Polq reverse transcriptase activity;
3. To investigate RNA-DNA repair using cellular and animal models. We anticipate that these studies will confirm
and characterize Polq RT activity in vitro and in a biological setting, and elucidate novel mechanisms of
mammalian RNA-DNA repair.

## Key facts

- **NIH application ID:** 10141272
- **Project number:** 5R01GM137124-03
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Richard T Pomerantz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,348
- **Award type:** 5
- **Project period:** 2020-04-08 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141272

## Citation

> US National Institutes of Health, RePORTER application 10141272, Mechanisms of RNA-DNA repair (5R01GM137124-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10141272. Licensed CC0.

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