# Molecular mechanisms of nucleic acid machines

> **NIH NIH R35** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $380,002

## Abstract

ABSTRACT
DNA replication is a fundamental process for all organisms to precisely duplicate genetic material prior to
cell division. Central to the process is a helicase enzyme that uses ATP-hydrolysis to separate base-paired
DNA to allow polymerases to gain access to synthesize complementary strands and also to drive the
replication machinery along the DNA. In human and other eukaryotic cells, the helicase engine is the 6-
protein MCM complex. The proposed research will fill a knowledge gap by providing atomic level
mechanism pictures of MCM proteins as they interact with ATP compounds and with DNA. These will be
studied at the molecular level by a coordinated approach involving structural studies by X-ray
crystallography and cryo-electron microscopy and also in vitro methods to study their functions and
interactions. The DEAD-box RNA helicase DDX3X has been implicated in many aspects of RNA
processing and is associated with several human diseases, including HIV, HCV, and medulloblastoma. The
proposed research will fill a knowledge gap by providing detailed pictures of DDX3X proteins interacting
with RNA and ATP compounds in the functional state. A considerable body of preliminary data has been
obtained for this project that includes the identification of a minimal fragment of DDX3X that has RNA-
stimulated ATPase activity and its crystal structure bound to relevant substrates.

## Key facts

- **NIH application ID:** 10839820
- **Project number:** 5R35GM136313-06
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Eric Enemark
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $380,002
- **Award type:** 5
- **Project period:** 2020-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839820

## Citation

> US National Institutes of Health, RePORTER application 10839820, Molecular mechanisms of nucleic acid machines (5R35GM136313-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10839820. Licensed CC0.

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