How cells detect DNA damage and activate ATR, ATM, and Fanconi anemia repair systems
Structural Mechanisms of DNA Damage Sensing and Activation of the ATR, Fanconi Anemia, and ATM Checkpoints
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 ID | NIH-11313820 on NIH RePORTER |
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.
Who could benefit from this research
Good fit: 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.
Not a fit: 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.
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 performed: 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
New York, United States
- 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
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 below.