How cells repair harmful DNA cross-links
Mechanism and regulation of DNA interstrand cross-link repair
This project looks at how cells fix DNA cross-links that can make some cancers resistant to chemotherapy and cause inherited bone marrow failure.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Harvard Medical School NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11187220 on NIH RePORTER |
What this research studies
DNA interstrand cross-links are lesions that bind the two DNA strands together and block normal copying of the genome. The team studies these events in the lab using frog egg extracts to capture detailed repair steps and then tests key findings in mammalian cells, focusing on proteins such as TRAIP, the CMG helicase, and the p97 enzyme. By watching how replication forks and repair machinery interact at a cross-link, they aim to map the sequence of events that allow cells to remove these lesions. Learning these steps could clarify why tumors become resistant to drugs like cisplatin and why people with Fanconi anemia fail to repair cross-links.
Who could benefit from this research
Good fit: People with cancers commonly treated with cross-linking chemotherapies (for example cisplatin) and individuals with Fanconi anemia are most directly connected to this research.
Not a fit: Patients whose conditions do not involve DNA cross-link damage or chemotherapy resistance are unlikely to gain direct benefit from this project.
Why it matters
Potential benefit: If successful, this work could reveal targets to make chemotherapy more effective and suggest new approaches for disorders like Fanconi anemia.
How similar studies have performed: Previous studies have identified many Fanconi anemia genes and core repair steps, so this project builds on established knowledge while exploring newer mechanisms like TRAIP-driven ubiquitylation that remain less understood.
Where this research is happening
Boston, United States
- Harvard Medical School — Boston, United States (Active)
Researchers
- Principal investigator: Walter, Johannes — Harvard Medical School
- Study coordinator: Walter, Johannes
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.