# Mechanisms of Action of UmuD in Regulating DNA Damage-Induced Genes in a umuC-Deficient Bacterium

> **NIH NIH R15** · MOREHEAD STATE UNIVERSITY · 2022 · $425,926

## Abstract

Project Summary
 Multi-drug resistant bacteria such as the ESKAPE pathogens are difficult to treat; finding new drug
targets and alternate methods of interfering with cell growth are crucial to infectious disease control. A
Gram-negative, nosocomial ESKAPE pathogen, Acinetobacter baumannii, has multiple antibiotic-resistance
genes and a mutagenic response to DNA damage that antibiotics can cause. The PI’s undergraduate research
team has uncovered a novel DNA damage response (DDR) system in this pathogen that uses a non-
canonical repressor, UmuDAb, and a small protein coregulator, DdrR, to repress mutagenic error-prone
polymerases. Typical DDR regulators, namely the LexA repressor of SOS genes and the SulA cell division
inhibitor, are not encoded by the non-enteric Acinetobacter genus, yet they possess a checkpoint response of
filamentation after DNA damage. There is increasing interest in targeting cell division and control
checkpoints to control bacterial infections, and novel mechanisms of cell division inhibition are recent
refinements to Escherichia coli and Bacillus DDR models. Staphylococcus aureus (also an ESKAPE pathogen)
and other Gram-positive and non-enteric bacteria that lack SulA instead use small proteins lacking inter-
genus homologies to inhibit cell division after DNA damage. Our team’s evidence suggests that the DdrR
component of SOS regulation mimics the actions of SulA and these Gram-positive growth inhibitors after
DNA damage: ddrR mutants have growth sensitivity to DNA damage and cannot inhibit cell division after it.
 This project’s long-term goal is to construct a new model of inhibiting cell division in Gram-negative
Gammaproteobacteria such as A. baumannii, which could help find non-antibiotic means of inhibiting its
growth and treating infectious disease. Our objectives are to identify how UmuDAb and DdrR directly and
indirectly control error-prone polymerase production and cell division checkpoints as part of the
Acinetobacter DDR. We hypothesize that the UmuDAb and DdrR regulators physically interact to control this
LexA-deficient pathogen's SOS response. Our objectives will be achieved using complementary approaches
to determine whether their phenotype of cell division inhibition results from directly interacting with
divisome proteins, or occurs through co-regulatory actions. Specifically, we will: (Aim 1) use biochemical
methods to identify UmuDAb-DdrR interactions; (Aim 2) establish these proteins' roles in inhibiting cell
division with fluorescence microscopy localization experiments, two-hybrid and growth inhibition assays;
and (Aim 3) examine previously obtained transcriptome data for targets of DdrR and UmuDAb regulatory
activities that may control DNA damage checkpoints and growth after DNA damage. The PI’s previously
demonstrated mutant strains, purified proteins, and expertise in microbiology, molecular biology,
biochemistry, and bioinformatics will allow her team of undergraduate students to complete thes...

## Key facts

- **NIH application ID:** 10360011
- **Project number:** 2R15GM085722-04
- **Recipient organization:** MOREHEAD STATE UNIVERSITY
- **Principal Investigator:** Janelle M Hare
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $425,926
- **Award type:** 2
- **Project period:** 2009-08-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360011

## Citation

> US National Institutes of Health, RePORTER application 10360011, Mechanisms of Action of UmuD in Regulating DNA Damage-Induced Genes in a umuC-Deficient Bacterium (2R15GM085722-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10360011. Licensed CC0.

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