SCD1 and SCD5 modulate PARP-dependent DNA repair via fatty acid desaturation in glioblastoma - PubMed
3 hours ago
- #DNA repair
- #fatty acid metabolism
- #glioblastoma
- SCD5 is identified as a critical driver in glioblastoma stem cell (GSC) maintenance and genomic stability, while SCD1's role in GBM is already established.
- SCD5 uniquely desaturates C18:0 and remodels sphingolipids, playing a non-redundant role compared to SCD1.
- Genetic silencing of SCD5 disrupts the cell cycle, impairs DNA repair, and triggers parthanatos (cell death due to PARP1 hyperactivation).
- Loss of SCD activity or saturated fatty acid accumulation leads to PARP1 hyperactivation, subsequent degradation, RAD51 depletion, compromised homologous recombination, and induction of parthanatos.
- Targeting SCD5 may offer a therapeutic strategy against therapy-resistant GSCs, enhancing efficacy of genotoxic or immunotherapeutic interventions.