# Mechanisms of DNA helicases and nucleases in genome maintenance

> **NIH NIH R35** · TRUSTEES OF INDIANA UNIVERSITY · 2021 · $66,377

## Abstract

Project Summary
Helicases and nucleases play important roles in maintaining genome integrity by
resolving intermediates produced during DNA metabolic processes, such as DNA
replication and repair. Recent studies suggest that genomic ribonucleotide
represents one of the most abundant DNA lesions in cells. In addition to the
ribonucleotides that prime DNA replication, significant amount of ribonucleotides
are mis-incorporated into the genome per cell cycle by replicating DNA
polymerases. In this proposal, using budding yeast as a model system, we
outlined research to define the roles of Srs2 helicase and its related nucleases in
the error-free removal of both priming and mis-incorporated genomic
ribonucleotides. Specifically, we will combine genetic, biochemical, and structural
approaches to define the mechanisms of Top1-catalyzed genomic ribonucloetide
excision repair with a focus on the Srs2-initiated error-free branch. In addition,
the potential role of Srs2 in lagging strand maturation will also be delineated.
Knowing that mutation of genes involved in ribonucloetide excision repair is
associated with Aicardi-Goutleres Syndrome and genome instability caused by
genomic ribonucloetide incorporation may increase the risk of cancer, our
research has direct disease relevance. In compliance with goal of MIRA award, we
will continue to tackle other key questions related to genome maintenance as we have
done in the past.

## Key facts

- **NIH application ID:** 10455810
- **Project number:** 3R35GM124765-05S1
- **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:** $66,377
- **Award type:** 3
- **Project period:** 2017-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455810

## Citation

> US National Institutes of Health, RePORTER application 10455810, Mechanisms of DNA helicases and nucleases in genome maintenance (3R35GM124765-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10455810. Licensed CC0.

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