The anillin-related Int1 protein and the Sep7 septin collaborate to maintain cellular ploidy in Candida albicans

Variation in cell ploidy is a common feature of Candida albicans clinical isolates that are resistant to the antifungal drug fluconazole. Here, we report that the anillin-related protein Int1 interacts with septins for coupling cytokinesis with nuclear segregation. Loss of Int1 results in a rapid disassembly of duplicated septin rings from the bud neck at the onset of actomyosin ring contraction. Strikingly, this has no major impact on cytokinesis and septum formation. However, Int1 genetically interacts with the Sep7 septin, maintaining the diffusion barrier at the bud neck and guarantying a faithful nuclear segregation. Indeed, int1ΔΔ sep7ΔΔ mutant cells, in contrast to int1ΔΔ cdc10ΔΔ, undergo a premature activation of mitotic exit prior to the alignment of the mitotic spindle with the division axis, producing large multinucleated cells. Some of these multinucleated cells arise from trimeras similar to those observed upon fluconazole exposure. Finally, the defects in nuclear segregation could be in part due to the inability to maintain the Lte1 mitotic exit activator at the cortex of the daughter cell. These results suggest that Int1 and Sep7 play a role in maintaining genome stability by acting as a diffusion barrier for Lte1.This work was supported by grants from the Spanish Ministry of Science and Innovation to CRV (BFU2010-15884 and BIO2015-70195-C2-1-R) and to JC-B (BFU2012-39910 and BIO2015-70195-C2-2R) and from the Junta de Extremadura to JC-B (GR15008). All Spanish funding is co-sponsored by the European Union FEDER programme. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. SOM was supported by pre-doctoral fellowships (FPI program) from the Spanish Government. The support and help of the Bioscience Applied Techniques Facility (Servicio de Técnicas Aplicadas a las Biociencias) of the University of Extremadura is greatly acknowledged.Peer reviewe