# Interplay between DNA base excision repair and transcriptional regulation

> **NIH NIH R35** · RESEARCH INST OF FOX CHASE CAN CTR · 2024 · $470,000

## Abstract

PROJECT SUMMARY
Guanine-rich G-quadruplex (G4) forming sequences are enriched at promoter proximal regions of the genome,
in particular those of cancer and DNA repair-related genes. These regions are hot spots for oxidative lesions
such as 8oxoG, coupling their repair via the base excision repair (BER) pathway to transcriptional regulation.
Unfortunately, the molecular level interactions and mechanistic details of the coupled repair and gene regulation
are not well understood, including the role of DNA structural dynamics, the precise mechanisms of repair and
gene activation, the role of the N-terminal intrinsically disordered region and redox mechanism of BER protein
apurinic/apyrimidinic endonuclease 1 (APE1).
My goal as the leader of my independent research program at Fox Chase over the next five years is to empower
and support a diverse team of young scientists to characterize the molecular-level interactions and coordination
events coupling the repair of oxidative DNA damage and gene enhancement at G4 promoters in response to
oxidative DNA damage. This will involve implementing a multi-disciplinary approach of techniques ranging from
structural biology and single-molecule fluorescence to cell-based assays.
By filling the current gaps in knowledge I will position my research program toward our long-term vision of
developing novel therapeutics that can modulate transcription of key disease-associated genes through
interfering with the key regulatory protein:protein and/or protein:DNA interactions.

## Key facts

- **NIH application ID:** 10940607
- **Project number:** 1R35GM155098-01
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** Amy Michelle Whitaker
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $470,000
- **Award type:** 1
- **Project period:** 2024-09-17 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940607

## Citation

> US National Institutes of Health, RePORTER application 10940607, Interplay between DNA base excision repair and transcriptional regulation (1R35GM155098-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10940607. Licensed CC0.

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