# Structure and Function of the Bacterial Primosome

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $277,655

## Abstract

DNA replication restart pathways reload cellular DNA replication complexes onto replication
forks that have been prematurely abandoned. These pathways form an essential link between
DNA repair (often recombinational repair) and replication. The proteins that drive these
reactions, referred to as the primosome or the Replication Restart Proteins, must recognize
the structures of abandoned replication forks and reload the DNA replication machinery
specifically at these sites. This process is heavily 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. Additionally, the mechanisms by
which replication restart pathways are integrated with core cellular DNA repair processes are
currently unknown. Our proposal combines structural, biochemical, and genetic approaches to
define the mechanisms of DNA replication restart in complementary ways. Our first overall
objective of this application is to determine the structural mechanisms that govern DNA
replication restart, from recognition of abandoned DNA replication forks, to primosome
assembly, and finally to reloading the first component of the DNA replication machinery. Aim 1
takes advantage of our preliminary data to define structural snapshots of each step in DNA
replication restart. Our second goal is to systematically define the genetic mechanisms that
support DNA replication restart. Aim 2 will identify the genes that coordinate double-strand DNA
break repair with replication restart and will define circumstances under which the major
replication restart pathways are utilized in cells. Additionally, the mechanisms underlying
replication restart suppressors will be examined.

## Key facts

- **NIH application ID:** 9962158
- **Project number:** 5R01GM098885-07
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** James L Keck
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $277,655
- **Award type:** 5
- **Project period:** 2012-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962158

## Citation

> US National Institutes of Health, RePORTER application 9962158, Structure and Function of the Bacterial Primosome (5R01GM098885-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962158. Licensed CC0.

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