# Structure and Function of the Bacterial Primosome

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $340,241

## Abstract

Abstract:
DNA replication restart pathways reload cellular DNA replication complexes onto
replication forks that have been prematurely terminated, forming an essential link
between DNA repair and replication. The proteins that drive these reactions, referred to
as the primosome or the Replication Restart Proteins, recognize the structures of
abandoned replication forks and reload the DNA replication machinery specifically at
these sites. The replication restart process is regulated to ensure loading fidelity and to
avoid over-replication that could arise from initiating replication at improper DNA
structures. In spite of the broad biological importance of this process, the mechanisms
underlying DNA replication restart and its regulation remain poorly understood. Our
proposal combines structural, biochemical, and genetic approaches to define the structural
and cellular mechanisms of DNA replication restart. Our overall objective is to determine
the mechanisms that govern each step of the process, from recognition of diverse
structures of abandoned DNA replication forks, to primosome assembly, and finally to
reloading the DNA replication machinery. Aim 1 will define the structures of primosome
complexes with replication forks, which will provide new insights into structure-specific
recognition of DNA replication forks and the mechanisms that regulate DNA replication
restart. Structural advances are coupled to genetic studies that will define the cellular
mechanisms of action of primosome proteins in bacteria. Aim 2 blends structural and
genetic studies to focus on maturation of primosome complexes and their activities in
reloading the replicative helicase back onto replication forks. Completion of our specific
aims will define the molecular and cellular mechanisms that mediate and regulate
bacterial DNA replication restart.

## Key facts

- **NIH application ID:** 10444289
- **Project number:** 2R01GM098885-09
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** James L Keck
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $340,241
- **Award type:** 2
- **Project period:** 2012-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444289

## Citation

> US National Institutes of Health, RePORTER application 10444289, Structure and Function of the Bacterial Primosome (2R01GM098885-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10444289. Licensed CC0.

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