Regulator of chromosome condensation

RCC1 (Regulator of Chromosome Condensation) is a guanine-nucleotide releasing factor that catalyzes the exchange of GDP for GTP on the small GTPase Ran (UniProt: P18754). This exchange is essential for Ran-mediated functions including nuclear import, cargo release from importins, and mitotic spindle assembly, with RCC1 maintaining high nuclear concentrations of GTP-bound Ran during the cell cycle.

RCC1 localizes to nucleosomes and double-stranded DNA, where it regulates the onset of chromosome condensation during S phase (UniProt: P18754). While primarily associated with mitotic and nuclear transport functions, a recessive mutation in RCC1 causes infection-induced acute-onset axonal neuropathy (IIAAN, MIM 621333), indicating broader relevance to neuronal integrity.

RCC1 is significantly upregulated in Alzheimer's disease brain tissue, with a mean log2 fold-change of 0.44 in post-mortem AD samples compared to age-matched controls across subcellular fractions (Chaparral AD proteomics). This upregulation may reflect altered nucleocytoplasmic transport or cell-cycle dysregulation commonly observed in AD pathology, though the specific mechanistic contribution requires further investigation.