# Helicase regulation during homologous recombination

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $363,164

## Abstract

Project Summary
Our chromosomes are continually bombarded with a variety of insults, resulting in damage that must be
repaired. By necessity, cells have evolved mechanisms to detect and repair broken strands of DNA,
thereby preventing loss of important genetic information. Double-stranded DNA breaks (DSBs) are a type
of damage that led to particularly disastrous outcomes. If not corrected, DSBs can lead to gross
chromosomal rearrangements, which are the hallmark of all forms of cancer. Indeed, defects in HR-
related proteins are associated with several severe genetic diseases. Patients with these diseases often
exhibit a strong predisposition for developing cancers due to a loss of genome integrity. Surprisingly,
DNA replication is the primary source of DSBs, and as a consequence rapidly growing cells are especially
dependent upon homologous DNA recombination for survival. This dependence upon homologous
recombination for the survival of rapidly growing cells highlights the potential for using recombination
inhibitors as highly selective cancer therapies. To fully exploit the clinical potential of homologous
recombination inhibitors it will be essential that we more fully understand the detail molecular
underpinnings of recombination and the proteins that are involved in regulating and controlling this
process.
 To help better understand the molecular basis of homologous DNA recombination we have developed
powerful new experimental platforms that allow us to directly visualize hundreds of individual DNA
molecules at the single molecule level. We are utilizing these unique research tools to probe the
fundamental basis for protein-nucleic acid interactions, with emphasis placed upon understanding
reactions relevant to human biology and disease. Here we will assess how ATP-dependent helicases can
exert “antirecombinase” activities and regulate homologous recombination by dismantling key
recombination intermediates. We will accomplish this goal by directly visualizing these processes in real-
time using optical microscopy. We will analyze factors that influence antirecombinase function and
specificity, we will determine precisely how antirecombinases dismantle recombination intermediates,
and we will seek to establish an understanding of common themes conserved among different eukaryotic
antirecombinases, as well as define the unique attributes of those proteins that are of particular importance
to human health. We will seek to determine detailed molecular information related to these questions, and
part of the significance of this project lies in the depth of the answers we strive to obtain.

## Key facts

- **NIH application ID:** 10358504
- **Project number:** 5R01CA236606-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Eric C Greene
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $363,164
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358504

## Citation

> US National Institutes of Health, RePORTER application 10358504, Helicase regulation during homologous recombination (5R01CA236606-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10358504. Licensed CC0.

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