Ipi3 is required for cell viability in Saccharomyces cerevisiae. Yeast Ipi3 has been reported to be an essential component of the Rix1 complex (Rix1-Ipi1-Ipi3) that is required for the processing of ITS2 sequences from 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication by interacting with ORC, MCM, Cdt1 and Cdc6. It has also been suggested that that human Ipi3 homolog plays a role in the assembly of the large ribosomal subunit in a computational analysis of large-scale protein-protein interactions.

Human Ipi3 is WDR18 (WD repeat domain 18), which is a member of the WD repeat protein family, and it shares significant homology with the yeast Ipi3; the identity is 22% and similarity is 40%. Since yeast Ipi3 has an important role in the initiati...[ Read more ]

Ipi3 is required for cell viability in Saccharomyces cerevisiae. Yeast Ipi3 has been reported to be an essential component of the Rix1 complex (Rix1-Ipi1-Ipi3) that is required for the processing of ITS2 sequences from 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication by interacting with ORC, MCM, Cdt1 and Cdc6. It has also been suggested that that human Ipi3 homolog plays a role in the assembly of the large ribosomal subunit in a computational analysis of large-scale protein-protein interactions.

Human Ipi3 is WDR18 (WD repeat domain 18), which is a member of the WD repeat protein family, and it shares significant homology with the yeast Ipi3; the identity is 22% and similarity is 40%. Since yeast Ipi3 has an important role in the initiation of DNA replication, it is possibly that hIpi3 also functions in the initiation of DNA replication in human cells.

We performed several experiments to support the hypothesis that hIpi3 is involved in the control of human DNA replication. First, knockdown of hIpi3 inhibited DNA replication, resulting in defective cell cycle progression. Second, the mRNA and protein levels of hIpi3 fluctuate in the cell cycle, just as some other pre-replicative (pre-RC) proteins do. Third, HA-tagged hIpi3 has been used to perform co-IP assay to identify hIpi3 interacting proteins. The results showed that hMcm7 interacted with hIpi3. Forth, hMcm7 and hCdc6 were reduced from chromatin after hIpi3 silencing, suggesting that hIpi3 is required for the chromatin association of the MCM complex. These results support that hIpi3 plays an important role in DNA replication in human cells.