# Dynamic functions of DNA2 counteract DNA replication stresses and tumorigenesis

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2023 · $122,195

## Abstract

Project Abstract
Phenotypic manifestation of cancer arises and further develops from genetic and epigenetic mutations, and a
potential source of these mutations is difficult to replicate (DTR) DNA sequences. These regions form DNA
secondary structures which must be resolved for DNA replication to progress fully. When cells are unable to
replicate DNA through these regions, genome instability may occur, which can lead to cancer initiation. Cells
contain proteins that allow DNA synthesis to occur faithfully through these regions, among which are the
nuclease/helicase DNA2 and the MutSα complex. Previous research has shown that these proteins both bind to
DNA secondary structures and that these proteins interact to drive resolution of these structures. Using the
Single Molecule Analysis of Replicated DNA (SMARD) technique, we will visualize the extent of DNA replication
in centromeres lacking DNA2, MSH2 or MSH6, components of the MutSα complex. Additionally, environmentally
contaminating compounds (ECCs) are known to bind to and stabilize these DNA secondary structures. We will
further use this technique to probe the impact of these compounds on DNA replication, which may reveal a
further source of genome instability. Altogether, our research will establish the role of DNA2 and the MutSα
complex on maintaining genome stability, explore the impact of putative DNA secondary structure stabilizing
compounds on DNA replication, and reveal a molecular basis for cancer manifestation and advancement.

## Key facts

- **NIH application ID:** 10801217
- **Project number:** 3R01CA085344-24S1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** BINGHUI SHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $122,195
- **Award type:** 3
- **Project period:** 1999-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801217

## Citation

> US National Institutes of Health, RePORTER application 10801217, Dynamic functions of DNA2 counteract DNA replication stresses and tumorigenesis (3R01CA085344-24S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801217. Licensed CC0.

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