RCC1

RCC1, short for Regulator of Chromosome Condensation 1, is a conserved nuclear protein that functions as the guanine nucleotide exchange factor (GEF) for the small GTPase Ran. By catalyzing the exchange of GDP for GTP on Ran, RCC1 establishes a high Ran-GTP concentration on chromatin. This Ran-GTP gradient is essential for directional nucleocytoplasmic transport, spindle assembly and function, and the reassembly of the nuclear envelope after mitosis.

Localization and structure: RCC1 is predominantly chromatin-associated and acts at the chromosomes to coordinate Ran signaling. It is a relatively large, modular protein typically described as a seven-bladed beta-propeller with an N-terminal extension that contributes to chromatin binding. The chromatin-bound localization positions RCC1 to directly regulate Ran activity where it is most needed for cargo transport and mitotic events.

Biological role: The Ran-GTP gradient generated by RCC1 on chromatin promotes release of cargo from import receptors and assembly factors from export receptors at appropriate cellular locations. This gradient also influences spindle microtubule dynamics and chromosome segregation during mitosis and aids in nuclear envelope reformation as the cell exits mitosis.

Genetics and evolution: The human RCC1 gene encodes the canonical RCC1 protein, and homologs or RCC1-like proteins exist across eukaryotes, often maintaining a similar role as RanGEFs with species-specific adaptations.

Clinical notes: Core components of the Ran pathway, including RCC1, are essential for cell viability. Dysregulation of RCC1 or its pathway can impact cell division and has been examined in the context of cancer biology and other diseases involving nuclear transport and mitosis.