# Mechanisms of regulation of DNA repair helicases

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $283,039

## Abstract

PROJECT SUMMARY / ABSTRACT
Helicases are a ubiquitous and highly diverse group of enzymes that separate the strands of nucleic acids and
are found in bacteria, eukaryotes, archaea, and many viruses. They are essential components of the genome
maintenance machinery. Their importance is highlighted in the many human disorders associated with defective
helicase function. Many helicases have been shown to carry out multiple, distinct functions in the cell. Often,
these processes place very different requirements on the helicase; for instance, one helicase may be tasked with
unwinding for short distances, long distances, or not at all, depending on context. How these different functions
are defined and regulated remains poorly understood.
 This project will focus on two proteins, UvrD and XPD, which serve as models for DNA repair helicases in
prokaryotes and eukaryotes, respectively. Although they are primarily involved in DNA repair pathways, both
helicases also participate in other cellular processes. UvrD and XPD are also prototypes for the two largest
structural classes of helicases known, and insights gained on their mechanisms are likely to extend to a number
of homologous systems. Prior studies have shown that helicase activity is strongly influenced by oligomeric and
conformational state. A monomer can exhibit low or no unwinding activity, but multiple molecules unwind
processively; helicases can unwind duplexes in one conformation but displace DNA-bound proteins in another.
Helicase roles have thus been proposed to be defined in the cell by protein partners controlling their oligomeric
and/or conformational state.
 These models remain speculative or have not been quantified adequately. In this project, we will investigate
the mechanisms by which helicase activity is regulated; first by understanding the factors that limit activity in
helicase monomers (Aim 1), next by measuring helicase oligomerization and quantifying how it enhances
unwinding activity (Aim 2), and lastly by studying helicase unwinding together with selected protein partners to
determine if they exploit the above strategies to regulate helicase activity (Aim 3).
 These aims will be achieved using a synthesis of single-molecule biophysical techniques—optical tweezers,
fluorescence microscopy, and microfluidics—together with traditional biochemical methods. These novel
approaches, which exploit the PIs' expertise, will be used to detect the unwinding of helicases at the single
molecule level, in real time, and at high resolution, while simultaneously measuring their oligomeric and
conformational state. Moreover, these techniques will enable the controlled assembly of multi-component
complexes. Beyond providing insights on helicase mechanism and the DNA repair pathways in which they
participate, our studies will advance biophysical methods for investigating the dynamics of biomolecular
complexes.

## Key facts

- **NIH application ID:** 9985883
- **Project number:** 5R01GM120353-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Yann R. Chemla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $283,039
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985883

## Citation

> US National Institutes of Health, RePORTER application 9985883, Mechanisms of regulation of DNA repair helicases (5R01GM120353-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985883. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*