How the BRCA1-A system helps repair broken DNA at stalled replication forks
The BRCA1-A complex function in DNA repair
This work looks at whether the BRCA1-A complex keeps damaged DNA stable in cancers with BRCA1, BRCA2, or ATM changes and how that affects response to drugs like PARP and topoisomerase I inhibitors.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11296677 on NIH RePORTER |
What this research studies
Researchers will use laboratory-grown cancer cells and biochemical models to see how the BRCA1-A complex binds to damaged DNA and nucleosomes at stalled replication forks. They will change genes, use cell imaging and electron microscopy, rebuild the BRCA1-A complex on chromatin, and analyze genome-wide data to track what happens when BRCA1-A is disrupted. The team is especially interested in how BRCA1-A behavior changes when ATM is mutated or inhibited and how that influences sensitivity or resistance to PARP and topoisomerase I drugs. Findings aim to explain why some tumors are hypersensitive or resistant to these therapies.
Who could benefit from this research
Good fit: Patients with cancers that carry BRCA1, BRCA2, or ATM mutations—or those whose doctors are using PARP or topoisomerase I inhibitors—are the most relevant group for these findings.
Not a fit: People whose cancers are driven by unrelated pathways or who do not have DNA repair–related mutations are less likely to see direct benefit from this specific work.
Why it matters
Potential benefit: If successful, the work could help predict which tumors will respond or resist PARP and topoisomerase I therapies and point to new ways to overcome resistance.
How similar studies have performed: PARP inhibitors are already effective in many BRCA-mutant cancers, but the specific role of the BRCA1-A complex in protecting stalled forks and driving resistance is a newer, actively studied idea.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Greenberg, Roger a — University of Pennsylvania
- Study coordinator: Greenberg, Roger a
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.