# Mechanisms of ATM activation by the MRN complex and DNA Double Strand Breaks

> **NIH NIH F32** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $62,261

## Abstract

Project Summary
DNA double stranded breaks (DSBs) are catastrophic events caused mainly by exposure to ionizing radiation
that can lead to mutations, chromosomal rearrangements, genome instability, and ultimately cancer. The MRN
protein complex and ATM kinase are central players involved in sensing a DSB and initiating a cellular
response that leads to either repair of the lesion, apoptosis, or senescence. Despite their known importance in
DSB sensing and repair, little is understood regarding how MRN assembles on DSBs, how ATP-driven
conformational changes in MRN aid in DSB repair, and how MRN recruits and activates ATM kinase. This
proposal seeks to utilize state-of-the-art cryogenic electron microscopy (cryo-EM) techniques, along with
rigorous biochemical assays to gain high-resolution structural and function insights into these key
processes. These studies will provide both a more complete understanding of this pathway, and will pave the
way for future structure guided drug design efforts targeting the MRN:ATM interaction in cancer cells.
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## Key facts

- **NIH application ID:** 10074132
- **Project number:** 5F32CA247320-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Christopher Warren
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $62,261
- **Award type:** 5
- **Project period:** 2020-02-01 → 2021-12-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074132

## Citation

> US National Institutes of Health, RePORTER application 10074132, Mechanisms of ATM activation by the MRN complex and DNA Double Strand Breaks (5F32CA247320-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10074132. Licensed CC0.

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