# Chemical Fingerprinting

> **NIH NIH R01** · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · 2020 · $655,621

## Abstract

The goal of the proposal is to determine whether DNA DSBR are killing neurons. DNA repair bas been linked
directly to Huntington Disease (HD) onset by genome-wide association studies (GWAS) in patients. CAG
expansion occurs in the process of repairing oxidative DNA damage, and its role for DNA repair was well
established in mouse models. During the past funding cycle, however, we have discovered that mhtt suppresses
DNA repair in brain cells in a cell-type and region-specific manner in the brains of HdhQ(150/150) animals. This
had modest effect on CAG expansion, but at the same time, resulted in the accumulation of DNA double strand
breaks (DSBs) that had gone undetected. DSBs are the most toxic of lesions, and if not repaired lead to cell
death. This raised the issue as to whether the unrepaired and previously unrecognized DSBs were responsible
for killing neurons. We have developed a new approach to defining DNA repair alterations in brain cells, called
repair fingerprinting. In Aim 1, we will use “repair fingerprinting” to determine whether DNA double strand breaks
are formed or repaired differently in astrocytes and neurons, and what pathways are involved. Repair
fingerprinting is an integrated three-arm approach to identify the landscape of DNA repair and extract which
pathways and machinery are responsible for the DSBR in brain cells. In Aim 2, we will determine whether cryptic
DNA double strand breaks are the primary driver of neuronal death in HdhQ(150/150) mice in vivo.

## Key facts

- **NIH application ID:** 9897402
- **Project number:** 2R01NS060115-12
- **Recipient organization:** UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
- **Principal Investigator:** Cynthia Therese McMurray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $655,621
- **Award type:** 2
- **Project period:** 2007-07-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897402

## Citation

> US National Institutes of Health, RePORTER application 9897402, Chemical Fingerprinting (2R01NS060115-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897402. Licensed CC0.

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