# Mechanisms of DNA helicases and nucleases in genome maintenance

> **NIH NIH R35** · TRUSTEES OF INDIANA UNIVERSITY · 2021 · $44,252

## Abstract

Project Summary
DNA damage presents a threat to genomic integrity and if unrepaired can contribute to
apoptosis or disease-causing mutations. Thus, accurate repair of lesions is necessary and
requires a team of repair enzymes. Topoisomerases are a class of DNA repair enzymes that
relieve torsional stress during a variety of DNA metabolic processes, such as replication and
repair. Type IA topoisomerases are best characterized for their decatenase activity, which in
yeast acts in concert with Rmi1 downstream of RecQ helicases. It has also been shown that
eukaryotic topoisomerase 3 (Top3; a type 1A topoisomerase) cleaves RNA molecules, but it is
unclear whether Top3 also possesses the genomic ribonucleotide excision function seen with
topoisomerase 1. In this proposal, we outline research aimed at understanding the substrate
requirements of yeast Top3 that promote efficient targeting and enzymatic activity. Further, we
plan to investigate the requirement for other proteins, such as the RecQ helicase and Rmi1, in
mediating Top3 substrate specificity. Because errors in DNA repair can contribute to
development of diseases, such as cancer, knowledge gained from the proposed studies can
provide insight into the role of type 1A topoisomerases in both normal and erroneous genomic
maintenance. Additionally, a number of cancer-associated mutations in the human type 1A
topoisomerase, TopoIIIa, have been collected. Thus, results from these studies could contribute
to a greater understanding of the role of type 1A topoisomerases in tumorigenesis.

## Key facts

- **NIH application ID:** 10168975
- **Project number:** 3R35GM124765-04S1
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** HENGYAO NIU
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,252
- **Award type:** 3
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168975

## Citation

> US National Institutes of Health, RePORTER application 10168975, Mechanisms of DNA helicases and nucleases in genome maintenance (3R35GM124765-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10168975. Licensed CC0.

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