# Replication Fork Repair

> **NIH NIH R01** · BRANDEIS UNIVERSITY · 2022 · $504,582

## Abstract

Project Summary
Replication fork repair is essential for cell survival and stability of genetic material. In humans,
inefficiency of repair is associated with cancer proneness, neurological, immunological,
developmental defects and premature aging. For microbial pathogens, the ability to repair DNA
damage is required for survival of bacterial pathogens and promotes genetic change that can
contribute to antibiotic resistance and persistence of infection.
The long-term goal of our studies is a more complete mechanistic understanding of the repair of
replication forks and how it affects genomic stability. This will be accomplished using the genetic
system of Escherichia coli, whose physiology is well understood. A central interest is how
bacterial cells signal difficulties in replication to facilitate repair and how this is integrated with
other aspects of bacterial growth. By biochemical and genetic analysis, this work will elucidate
how a newly discovered conserved DNA helicase protein, YoaA, interacts with the replisome to
overcome barriers in replication. This study will specifically address the influence of RNA
transcription and DNA protein complexes on replication and genomic instability and what
mechanisms are used to overcome conflicts between replication and transcription machinery.
The regulatory pathway controlled by stringent starvation protein, SspA, will also be explored to
discover how it impacts DNA metabolism.
Because all cells repair DNA in fundamentally similar ways by evolutionarily related pathways,
these studies using microbial model organisms should reveal mechanisms applicable to repair
of DNA in human cells. In addition, because the DNA damage response in microbial pathogens
plays a role in toxin production, antibiotic resistance and persistence of infection, this work could
provide new information important for the treatment of infectious disease.

## Key facts

- **NIH application ID:** 10522340
- **Project number:** 2R01GM051753-25A1
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** SUSAN THOMAS LOVETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $504,582
- **Award type:** 2
- **Project period:** 1994-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522340

## Citation

> US National Institutes of Health, RePORTER application 10522340, Replication Fork Repair (2R01GM051753-25A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10522340. Licensed CC0.

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