FANCA-dependent FEN1 recruitment suppresses transcription-replication conflicts and PARPi sensitivity - PubMed
3 hours ago
- #FANCA
- #PARP inhibitor
- #transcription-replication conflict
- FANCA deficiency drives tumor progression and PARP inhibitor synthetic lethality in diverse cancer models.
- Loss of FANCA disrupts FEN1 recruitment to replication forks, impairing Okazaki fragment maturation and causing single-strand DNA gaps.
- FANCA deficiency leads to RPA exhaustion under PARP inhibitor treatment, even in homologous recombination-proficient cells.
- FANCA loss promotes transcription-replication conflicts on the lagging strand, sensitizing cells to PARP inhibitors.
- Inhibition of RNA polymerase II or overexpression of RNase H can reverse PARP inhibitor sensitivity caused by FANCA deficiency.