# DNA damage response and repair of a broken chromosome

> **NIH NIH R35** · BRANDEIS UNIVERSITY · 2020 · $945,007

## 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 carry our repair of
chromosomal double-strand breaks (DSBs). Using budding yeast as a model system, it is possible
to induce site-specific DSBs with a high degree of synchrony not yet possible in mammalian cells,
allowing “in vivo biochemistry” approaches to monitor intermediate steps in DSB repair and DNA
damage signaling. The first of three foci of this proposal investigates key questions concerning
DSB repair by homologous recombination. How are homologous donor sequences found and
used to repair a DSB? How are mismatches tolerated and repaired during different steps of
recombination? How do cells deal with chromatin during repair and how is chromatin re-
established after repair is complete? And how is gene editing accomplished using single-stranded
DNA templates? The second area seeks to understand what is 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. The third main objective is to understand how the DNA damage
checkpoint and DNA damage-induced autophagy are regulated. We wish to determine: How does
the DNA damage response affect DSB repair? How is the DNA damage checkpoint maintained
and how is autophosphorylation of Mec1ATR regulated? What is the basis of a regulatory hand-off
between the damage response and the spindle assembly checkpoint? Finally, we will determine
the targets of DNA damage-induced autophagy and how autophagy contributes to cell cycle arrest
in response to even a single unrepaired DSB. These studies will provide new insights and
guidance in defining the DSB repair and checkpoint signaling in human cells.

## Key facts

- **NIH application ID:** 9970282
- **Project number:** 5R35GM127029-03
- **Recipient organization:** BRANDEIS UNIVERSITY
- **Principal Investigator:** JAMES E HABER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $945,007
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970282

## Citation

> US National Institutes of Health, RePORTER application 9970282, DNA damage response and repair of a broken chromosome (5R35GM127029-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9970282. Licensed CC0.

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