# DNA damage response and repair of a broken chromosome

> **NIH NIH R35** · BRANDEIS UNIVERSITY · 2024 · $102,020

## Abstract

PROJECT SUMMARY
The overall goal of NIGMS-funded research in my lab is to describe the molecular and cellular
mechanisms by which cells sense the presence of DNA damage and how they repair
chromosomal double-strand breaks (DSBs). Primarily using budding yeast as a model system, it
is possible to induce site-specific DSBs with a high degree of synchrony that is not generally
possible in mammalian cells, allowing “in vivo biochemistry” approaches to monitor intermediate
steps in DSB repair and DNA damage signaling. We also wish to apply our understanding of DNA
repair and recombination mechanisms to elucidate how the Lyme disease bacterium, Borrelia
burgdorferi, is able to “change its coat” by repeated gene conversion events.
The goals for the next five years of this project focus on understanding how homologous donor
sequences are found and used to repair a DSB and how mismatches are tolerated and repaired
during different steps of recombination. A second objective is to understand the basis of the 1000-
fold increase in mutations associated with DSB repair and how microhomologies are used in
repair-dependent template switching, creating complex chromosome rearrangements analogous
to events recently found in human cancers. We employ similar approaches to elucidating how
CRISPR/as9-mediated gene editing is accomplished using single-stranded DNA templates. A
third area of concern is to understand how the DNA damage checkpoint is regulated. We wish to
determine how the DNA damage response affects DSB repair and how the DNA damage
checkpoint is maintained and turned off. These studies will provide new insights and guidance in
defining the DSB repair and checkpoint signaling in human cells.
Finally, we will continue our investigation of the mechanisms by which Borrelia initiates and
mediates gene conversion events between one expressed gene and a set of adjacent
pseudogenes.

## Key facts

- **NIH application ID:** 11053151
- **Project number:** 3R35GM127029-07S1
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** JAMES E HABER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $102,020
- **Award type:** 3
- **Project period:** 2018-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11053151

## Citation

> US National Institutes of Health, RePORTER application 11053151, DNA damage response and repair of a broken chromosome (3R35GM127029-07S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11053151. Licensed CC0.

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