# A Dynamic Perspective of the DNA Damage Response

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $50,520

## Abstract

ABSTRACT
The DNA damage repair mechanism is highly dynamic, with many interacting components. However, it
remains unclear how various repair modules dynamically interact. A greater understanding of these
mechanisms could allow us to maximally leverage these dynamics for therapeutic benefit. I have developed an
innovative high-throughput screening technique, Genome-Wide Dynamic Evaluation (GEoDE), that couples
high-density 6,144 colony yeast colony genetic mutant arrays with time-lapse imaging to achieve genome-
wide, time-resolved fitness screens which may be used to screen multiple therapeutic agents against
thousands of colonies in real time. Analysis of the UV-induced DNA damage response using this technique has
elucidated the dynamic sequencing of UV response pathways in yeast and identified 175 novel UV-responding
genes. Importantly, GEoDE can identify the time at which each gene is needed in the recovery from UV-
induced damage. These findings suggest that genetic fitness landscapes are dynamic and contain valuable
time and condition-specific information. An additional tool built by our lab, systematic-gene-to-phenotype arrays
(SGPA), permits interrogation of genetic landscapes behind given phenotype. This proposal uses GEoDE and
SGPA to build a complete model of the dynamic response to DNA damage, first via genome-wide screens in
the genetically tractable model organism S. cerevisiae (Aim 1), and then via targeted screens in human cell
lines (Aim 2). The ultimate goal is to identify specific therapeutic targets and treatment windows in the DNA
damage response pathway.

## Key facts

- **NIH application ID:** 9932791
- **Project number:** 5F30CA236404-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Erica Nicole Silva
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932791

## Citation

> US National Institutes of Health, RePORTER application 9932791, A Dynamic Perspective of the DNA Damage Response (5F30CA236404-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932791. Licensed CC0.

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