# Functions of DNA helicases at hard-to-replicate sites and telomere regulation

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $388,750

## Abstract

Abstract
The overall objective of this proposal is to answer two fundamental questions on DNA
metabolism: 1) how DNA replication progresses timely and efficiently at hard-to-replicate sites;
and 2) how the large nucleoprotein complexes that comprise telomeres, the end of linear
chromosomes, are assembled and regulated. The first question emerges from our ongoing
mechanistic studies on the conserved Pif1-family of helicases. Our work highlights the
fundamental role that these helicases have in facilitating DNA replication at both secondary
DNA structures and protein barriers. Going forward, we seek to address the following: what
mechanisms couple the helicase activity to DNA synthesis by polymerases; how this synergy
leads to removal of obstacles imparted by protein barriers encountered in the nucleus or in
mitochondria; whether removal of obstacles is a general property of this class of helicases. The
second question is novel and is based on our recent finding of new properties of both yeast and
human telomere DNA binding proteins; namely, the ability of these proteins to interact with
telomeric DNA repeats in alternative modes and to facilitate DNA condensation. Our goal is to
test whether these properties play a role in establishing telomere length discrimination and
accessibility. We tackle these problems by using biochemically reconstituted systems and
employing a multipronged approach that integrates ensemble biochemical and biophysical
techniques with single-molecule methods, thus providing unparalleled access to the behavior of
individual molecules.

## Key facts

- **NIH application ID:** 10906128
- **Project number:** 5R35GM139508-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Roberto Galletto
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2021-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906128

## Citation

> US National Institutes of Health, RePORTER application 10906128, Functions of DNA helicases at hard-to-replicate sites and telomere regulation (5R35GM139508-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906128. Licensed CC0.

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