pka1 deletion induces hyperactivation of the transcription factor Mca1 and drives chromosome mis-segregation in Schizosaccharomyces pombe.

The cAMP-dependent protein kinase (PKA) pathway is required for proper chromosome segregation in Schizosaccharomyces pombe. Deletion of pka1 gene causes chromosome mis-segregation and sensitivity to microtubule-depolymerizing drugs. We have previously identified rst2∆, tfs1∆, mca1∆, and moc3∆ as suppressors of the pka1∆ phenotype, implicating transcriptional-related factors in the process. In the present study, we show that mca1 deletion suppresses both TBZ sensitivity and chromosome mis-segregation in pka1∆ cells. Mca1 contains an N-terminal DNA-binding domain that is required for suppression of TBZ sensitivity in the pka1∆ strain. Mca1 expression levels were higher in pka1∆ cells than in wild-type cells, and overexpression of Mca1 induced TBZ sensitivity and a high frequency of chromosome mis-segregation, indicating that appropriate Mca1 protein levels are critical for accurate chromosome segregation. The combined deletion of mca1, rst2, and tfs1 resulted in stronger suppression of TBZ-induced growth inhibition in pka1∆ cells compared with any single deletion, suggesting that these factors function in parallel or partially independent pathways rather than in a single linear pathway. Consistently, the high frequency of chromosome mis-segregation observed in pka1∆ cells was reduced by combinations of mca1∆, tfs1∆, and rst2∆, with tfs1∆ showing the strongest, mca1∆ moderate, and rst2∆ the weakest suppressive effects. Taken together, these findings demonstrate that transcriptional mis-regulation mediated by Mca1, Tfs1, and Rst2 contributes to defective chromosome segregation in the absence of functional Pka1.