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

WRN helicase (PDB: 2QZ2) — Walker A/B and Sensor 1 motifs coordinate ADP–Mg²⁺ in the post-hydrolysis state. C-terminal tail (L514) couples helicase and exonuclease activities.

WRN loss → Werner syndrome + simultaneous acceleration of telomere attrition, epigenetic dysregulation, and stem cell exhaustion. A structural window into multi-hallmark aging.

#WRN #WernerSyndrome #StructuralBiology #LongevityBiology #DNARepair #Biogerontology #AgingHallmarks

PARP1 (PDB: 4DQY) — catalytic core resolves NAD⁺ positioning (H133/E134/Mg²⁺) and substrate interface (326–332) as structurally separable sites. E134 as the ADP-ribose acceptor base.

Age-associated DNA damage → PARP1 hyperactivation → NAD⁺ depletion → SIRT1/3 inactivation → mitochondrial dysfunction. A structurally grounded feedforward loop in biological aging.

#PARP1 #NAD #StructuralBiology #LongevityBiology #Aging #DNARepair #Biogerontology #Sirtuins