FIG. 7.

Model for DmRfc4 mutant phenotypes in mitosis. The mitotic phenotypes observed when DmRfc4 is mutated can be classified in two categories, that of PCC-like and that of PSCS figures. In wild-type cells, a block to replication or presence of DNA damage would result in cell cycle arrest, as the signal is passed through a phosphorylation cascade, resulting ultimately in inhibition of CDK1 activity and preventing entry into mitosis. In Rfc4 mutants, this arrest is not accomplished and cells proceed into mitosis. (A) Development of PCCs. PCC is a state of mitotic catastrophe resulting from the premature condensation of chromatin during S or G₂ phase without the completion of DNA replication and/or the repair of damaged DNA. (B) Development of PSCS. This mitotic phenotype may result from abnormal progression through mitosis, possibly due to an aberrant structure at the kinetochore. A normal centromere (open circle) properly mediates spindle attachment and chromosome segregation. Improperly replicated centromeres may not accurately assemble centromeric proteins. Therefore, the lack of attachment between the sister chromatids and the spindle observed during metaphase results in lagging chromatids during anaphase. Micronuclei are formed from the inaccurately segregated chromosomes.