# The role of cysteines in the response of 8-oxoguanine glycosylase (OGG1) to oxidative stress

> **NIH NIH K99** · UNIVERSITY OF ARIZONA · 2020 · $98,793

## Abstract

Project Summary/Abstract: Oxidative stress caused from exposure to environmental toxins results in DNA
damage that is repaired by the DNA repair machinery. 8-oxoguanine (8-oxoG) is the most commonly formed
DNA lesion, which is recognized and removed by 8-oxoguanine glycosylase (OGG1). The function of OGG1 is
important to prevent propagation of DNA error and to mediate transcription of genes responsible for the
response to oxidative stress. The inability of cells to perform these tasks can lead to autoimmune and
neurodegenerative diseases, cancer, and aging. In addition to DNA oxidation, cysteines can also be targeted
for oxidative modification under oxidative stress. OGG1 contains 8 cysteine residues which are potentially
targeted for modification in the presence of environmental toxins. This proposal seeks to elucidate the role of
cysteine in OGG1 in DNA repair and transcription in response to oxidative stress. Biochemical characterization
of OGG1 cysteine mutants is proposed in specific aim 1 to look at the function of cysteine in DNA binding,
enzymatic activity, conformational changes, and in protein-protein interactions. These studies will be initiated
during the K99 mentored phase and then continued independently during the R00 phase. The second aim will
focus on in vivo cell culture work to understand the role of cysteine in DNA repair and in gene regulation and
also to identify OGG1 modifications resulting from environmental toxin treatment. The proposed work in this
aim will be initiated during the mentored phase, and the technical expertise gained during the mentored phase
will be employed during my independent work to accomplish the proposed goals. This work will clarify the role
of OGG1 modification in disease initiation and progression and will help in predicting the biological effect of
toxin exposure. This work will also provide a foundation for targeted drug design. The long-term goal for this
award is to transition into an independent academic research program to explore the comprehensive molecular
mechanism of the DNA damage response under oxidative stress and how modifications in the DNA repair
machinery lead to disease. To achieve the goals of this award, I assembled a team of mentors with expertise in
environmental science, proteomics, redox biochemistry, DNA glycosylases, DNA repair, and gene
transcription. This team will also provide me with mentoring in career development for transitioning into
independence and establishing and running a successful lab. Further training will be acquired from attending
special topic workshops and courses on grant writing and career development offered both at and outside of
Yale University. Additional opportunities to attend and present at conferences and to mentor students and
postdocs along with continued preparation of manuscripts will be complementary for my long-term goal of
establishing an independent research program. These tools will be essential to gain technical training and for
ca...

## Key facts

- **NIH application ID:** 9980416
- **Project number:** 5K99ES029555-03
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Khadijeh Alnajjar
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $98,793
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980416

## Citation

> US National Institutes of Health, RePORTER application 9980416, The role of cysteines in the response of 8-oxoguanine glycosylase (OGG1) to oxidative stress (5K99ES029555-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980416. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*