Wednesday, February 18, 2026 2/18/2026

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

Award Number: R21DE030411
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2023

Group Awards By:

View Award Description

Mechanisms for the repair of oxidative stress-induced DNA damage in Porphyromonas - 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 stability in anaerobes exposed to environmental stress. These components could be targets for the development of novel therapeutic interventions for the control and prevention of P. gingivalis-associated diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	LOMA LINDA UNIVERSITY	11145 ANDERSON ST STE 203	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	000	2	3/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $197,500 )
2022	2022	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	001	2	7/5/2022	NON-COMPETING CONTINUATION	$0
2022	2022	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	000	2	6/30/2022	NON-COMPETING CONTINUATION	$197,500
														Subtotal = $197,500

Issue Date FY: 2021 ( Subtotal = $237,000 )
2021	2021	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Oral Diseases and Disorders Research	000	1	6/30/2021	NEW	$237,000
														Subtotal = $237,000

Grand Total All Awards = $434,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

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

Award Number: R21DE030411

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer