Cran1, member of a new class of OLD family ATPases, functions in cell cycle progression in an archaeon

Overcoming lysogenization defect (OLD) proteins are diverse ATPase-nucleases functioning in antiphage defense in bacteria. However, the role of these proteins in archaea is currently unknown. We describe a new class of archaeal OLD family ATPases and show that they are apparently not involved in antiviral defense but play an essential role in cell cycle progression. The gene for an OLD family enzyme in Saccharolobus islandicus REY15A, named here Cran1 (Cell cycle-related ATPase and nickase 1), cannot be deleted and exhibits cyclic expression patterns at transcriptional and translational levels, with peak expression during the transition from M-G1 to S phase. Cran1 overexpression causes significant growth retardation, cell size enlargement, and increased cellular DNA content. Cran1 displays potent nickase and ATPase activities in vitro, with the nickase activity dependent on the presence of the ATPase domain. Notably, Cran1 copurifies with chromatin-associated proteins, such as Cren7 and a histone deacetylase homolog, suggesting its involvement in chromatin-related activities. Collectively, our results suggest that Cran1 plays an important role in cell cycle progression, revealing a novel function of OLD family proteins.