# Mechanisms for the repair of oxidative stress-induced DNA damage in Porphyromonas

> **NIH NIH R21** · LOMA LINDA UNIVERSITY · 2021 · $237,000

## Abstract

Porphyromonas gingivalis, as a “keystone pathogen”, highlights its ability to adapt to the harsh inflammatory
conditions of the periodontal pocket. Because the environmental stress response is a major determinant of its
virulence, it is our long-term goal to gain a comprehensive understanding of its survival strategy(s). DNA
damage is a major consequence of oxidative stress. While more than 20 different oxidatively altered bases
might be generated by this stress, 8-oxo-7,8-dihydroguanine (8-oxoG) is one of the most common product of
DNA damage. Guanine is the most susceptible base to oxidation and forms mainly 8-oxoG due to its low redox
potential. In prokaryotic cells the presence of 8-oxoG is mainly repaired by base excision repair (BER). A
survey of the P. gingivalis genome indicate that an important component of the BER system is missing. Because
the average G + C content of the genome of P. gingivalis is 49%, a mechanism(s) to prevent or repair lesions
resulting from guanine oxidation is vital. There is a gap in our comprehensive knowledge on a mechanism(s) for
the repair of oxidative stress-induced DNA damage in P. gingivalis. We have previously demonstrated that there
is an accumulation of 8-oxoG in the chromosome of P. gingivalis exposed to H2O2-induced oxidative stress.
Neither BER nor nucleotide excision repair (NER), as observed in other strains, appear to be involved in the
repair of the 8-oxoG lesion in P. gingivalis. DNA affinity fractionation identified PG1037, a conserved hypothetical
protein, among others, that were preferentially bound to the oligonucleotide fragment carrying the 8-oxo-G lesion.
PG1037 is part of the uvrA-pg1037-pcrA operon in P. gingivalis which is known to be upregulated under H2O2-
induced stress. The purified recombinant PG1037 protein, likely via a reducing function, has the ability to prevent
Fenton chemistry-mediated DNA damage in vitro and, under oxidative stress conditions, reduced the cleavage
of the 8-oxoG lesion by the E.coli foramidopyrimidine glycosylase (Fpg) enzyme. In silico analysis of PG1037
shows a protein that contains a zinc finger domain, two peroxidase homologous motifs and a cytidylate kinase
domain. The goal of the proposal is to test the hypothesis that a novel P. gingivalis protein (PG1037)
carrying peroxidase motifs and a zinc finger domain is involved in the repair of oxidatively damaged
DNA. Our aims are to confirm the specific role of PG1037 in the removal of 8-oxoG from duplex DNA and to
evaluate any interaction of PG1037 with other proteins in that process. The data will provide a major conceptual
advance on the molecular bases for the repair of oxidative stress-induced DNA damage in P. gingivalis and
could likely support a unique and effective DNA repair mechanism we propose to designate “base redox repair”.
It will set the stage, in a future RO1 application, to address specific structure-function questions on the vital
components and their corporation in maintaining genomic st...

## Key facts

- **NIH application ID:** 10174514
- **Project number:** 1R21DE030411-01
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **Principal Investigator:** Hansel M. Fletcher
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174514

## Citation

> US National Institutes of Health, RePORTER application 10174514, Mechanisms for the repair of oxidative stress-induced DNA damage in Porphyromonas (1R21DE030411-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10174514. Licensed CC0.

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