The Saccharomyces cerevisiae protein SRM1 and the mammalian protein RCC1 have amino acid sequence similarity throughout their lengths. SRM1 was defined by a recessive mutation in yeast that both activates the signal transduction pathway required for mating and leads to arrest in the G1 phase of the cell cycle. RCC1 was defined by a recessive mutation in hamster cells that causes premature chromosome condensation and other characteristics of entry into mitosis. Despite the seemingly different roles implied by these phenotypes, we suggest that RCC1 and SRM1 proteins have similar functions. In particular, we find that RCC1 can complement the temperature-sensitive growth phenotype of two independent srm1 mutations and also complements, at least partially, phenotypes associated with activation of the pheromone response pathway, such as transcription induction of FUS1. However, RCC1 fails to complement an srm1 null allele. Further characterization of the srm1 mutant phenotype reveals a defect in plasmid and chromosome stability, suggesting that the mutants have a defect in DNA replication, mitosis, or their coordination. Finally, like RCC1, SRM1 is a nuclear protein. Together, these data imply that SRM1 and RCC1 have a common role in their respective organisms.