How cells detect DNA damage and activate ATR, ATM, and Fanconi anemia repair systems
Official title: Structural Mechanisms of DNA Damage Sensing and Activation of the ATR, Fanconi Anemia, and ATM Checkpoints
Funded at Sloan-Kettering Inst Can Research · NIH-11313820 · Data updated 2026-11-12
Researchers are using high-resolution structural imaging to show how key repair proteins sense DNA damage, with relevance for people whose cancers come from DNA repair defects.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sloan-Kettering Inst Can Research NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project start | August 1, 2023 |
| Project end | April 30, 2027 |
| Funding year | 2026 |
| Award (this year) | $672,595 |
| NIH project number | 5R01GM149915-04 |
| Project ID | NIH-11313820 on NIH RePORTER |
Who could benefit from this research
✓Could help
People most directly connected would be patients with cancers or inherited conditions linked to ATM, ATR, or Fanconi anemia pathway mutations who might eventually benefit from targeted therapies arising from this work.
✕Less likely to help
Patients seeking immediate clinical treatment or those whose cancers are unrelated to DNA repair pathway defects are unlikely to benefit directly from this basic structural research in the short term.
What this research studies
This project uses cryo-electron microscopy to create detailed 3D images of the protein assemblies (ATR, ATM, and Fanconi anemia complexes) that sense DNA damage. The team will reconstitute these assemblies, visualize how they bind damaged DNA and interact with each other, and compare normal versus disease-linked variants. By revealing the molecular switches that trigger cell-cycle arrest and repair, the work aims to explain how failures in these pathways lead to genetic instability and cancer. The structural maps could point to new drug targets or strategies to restore proper DNA repair in affected patients.
Why it matters
Potential benefit: If successful, this work could identify molecular targets for new therapies and improve understanding of cancers caused by DNA repair defects.
How similar studies have gone: Cryo-EM and biochemical studies have already revealed structures of several DNA repair complexes, but key assemblies and the exact effects of many disease-linked mutations on ATR/ATM/Fanconi machinery remain largely unresolved.
Where this research is happening
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Sloan-Kettering Inst Can Research
New York, United States Active
Researchers
- Principal investigator: Pavletich, Nikola P — Sloan-Kettering Inst Can Research
- Study coordinator: Pavletich, Nikola P
Related research
Other NIH-funded projects on the same topics.
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In vivo gene repair to restore healthy hematopoiesis in Fanconi anemia
A study aims to repair faulty genes inside patients’ blood-forming cells to help people with Fanconi anemia regain healthy blood cell production.
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Understanding genetic dependencies when Fanconi anemia pathway is lost
A study to find other genes or pathways that cancer cells rely on when the Fanconi anemia repair system is broken, with the aim of guiding future treatments.
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Innovative cell and gene therapy approaches to treat Fanconi anemia
A Stanford-led project aims to develop safer cell and gene therapies to help people with Fanconi anemia who have bone marrow failure.
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In vivo gene therapy for Fanconi anemia
A patient-focused overview of a potential in vivo gene therapy approach to correct Fanconi anemia, aiming to reduce the need for donor transplants.
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Fanconi anemia: what happens inside cells
Researchers want to learn how proteins called REV7 and CHAMP1 change DNA repair in people with Fanconi anemia and related genetic syndromes.
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Understanding how cells detect and respond to DNA damage
This study is looking at how our cells detect and fix damage to their DNA, which is really important for stopping cancer, and it aims to understand how certain proteins work together to repair serious DNA problems, with the hope that this knowledge can help develop new treatments to improve DNA repair in cancer cells.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.