FANCM (PDB: 5V5X) — DEAD-box ATPase geometry (K1175/Mg²⁺) drives replication fork reversal at interstrand crosslinks, not classical duplex unwinding. Helicase–DNA interface: residues 1290–1297.
Fork reversal fidelity declines with age. FANCM's structural landscape is an underexplored target in replication stress and genomic aging.
#FANCM #FanconiAnemia #StructuralBiology #DNARepair #ReplicationStress #LongevityBiology #Biogerontology
Huge congratulations to @EZ_eta for leading the experimental work, and a big thank you to our collaborators at IIT for their Nanopore expertise, as well as to Michele Giannattasio head of the EM on Single Molecules Facility for his contribution to the structural analysis.
#eccDNA #ecDNA #CancerResearch #GenomeInstability #DNARepair #ReplicationStress
How do cancer-associated extrachromosomal circular DNAs arise?
In our new manuscript, we show that single-strand DNA damage in repetitive sequences can trigger i-loop formation and eccDNA generation. What started at telomeres may reflect a much broader principle across the genome and help explain how ecDNA may emerge in cancer.
https://authors.elsevier.com/a/1n0wG3vVUPZO38
#eccDNA #ecDNA #CancerResearch #GenomeInstability #DNARepair #ReplicationStress
Alice Frolov
Lab Doksani