# Structural basis of replisome mediated DNA replication and repair

> **NIH NIH R35** · RICE UNIVERSITY · 2021 · $384,289

## Abstract

DNA is the blueprint of life and DNA replication and maintenance are essential for human health.
Damages on DNA due to endogenous or environmental assaults can hamper DNA replication and
induce genome abnormities and human diseases. A replisome is a multi-protein complex responsible
for DNA replication. Moreover, as the first one to meet any replication barrier, the replisome plays
essential roles in signaling replication stress and facilitating DNA repair. However, the structural basis
of replisome operation and replisome mediated replication stress response and repair remains unclear.
We propose to use biochemical reconstitution and cryo-EM structural determination to investigate how
the replisome acts under normal and stressed conditions and how disfunction of the replisome leads to
genetic variations and human diseases. First, we will employ replisome from bacteriophage T7 as a
model system to investigate the structural basis of replisome operation under stressed conditions. I
have recently obtained the first structure of the T7 replisome operating on its DNA substrate, which
illustrated the organization and the working mechanism of a replisome. We will further investigate how
the T7 replisome responses to various replication barriers to trigger appropriate replication-coupled
repair. Second, we will investigate the structural basis of mitochondria DNA replication. Mitochondria
is the power house of a cell and errors on mitochondria DNA due to faulty DNA replication are
connected to many human genetic diseases. We will reconstitute the mitochondria replisome and
investigate how mitochondria DNA is replicated and how mutations on mitochondria replisome lead to
human diseases. Our investigations will provide the first structural framework for understanding
replisome mediated DNA replication, stress response and repair. The structural information will
contribute to the development of novel therapies to target or avoid targeting DNA replication.

## Key facts

- **NIH application ID:** 10275032
- **Project number:** 1R35GM142722-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Yang Gao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,289
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275032

## Citation

> US National Institutes of Health, RePORTER application 10275032, Structural basis of replisome mediated DNA replication and repair (1R35GM142722-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275032. Licensed CC0.

---

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