AI Insight
This study reveals that G-quadruplex (G4) DNA structures facilitate homologous recombination by promoting template strand invasion during DNA repair. The researchers found that the helicase DHX36 normally suppresses this process by unwinding G4 structures, and when DHX36 is lost, stabilized G4s enhance recombination efficiency and accelerate repair of replication-associated breaks. Loss of DHX36 can partially rescue DNA repair defects in BRCA1-deficient cells but also promotes aberrant recombination events.
Why it matters
These findings could inform new therapeutic strategies for cancer treatment, particularly for BRCA1-mutant tumors that are resistant to PARP inhibitors. Understanding how G4 structures regulate DNA repair fidelity may help develop targeted interventions that enhance beneficial recombination while preventing harmful genomic rearrangements.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Homologous recombination (HR) requires efficient homology search and strand invasion, yet how homologous templates are identified within the nucleus remains unclear. Here, we identify G-quadruplex (G4) DNA structures as pervasive effectors of template strand invasion and uncover the G4 helicase DHX36 as a potent suppressor of this process. DHX36 loss stabilizes G4s, enhances HR, and accelerates repair of replication-associated DNA breaks. G4-mediated HR depends on the non-canonical strand invasion factors RAD51AP1, WDR48, and USP1, and requires G4 motifs within the homologous repair template. DHX36 loss partially restores HR and PARP inhibitor resistance in BRCA1-deficient cells, while promoting aberrant recombination and Alternative Lengthening of Telomeres (ALT). Together, our findings establish dynamic G4 regulation as a key determinant of homology search, genome maintenance, and recombination fidelity.
Source: G quadruplex DNA facilitates a pervasive path to homologous recombination