The N-Terminal Region of the Polo Kinase Cdc5 Is Required for Downregulation of the Meiotic Recombination Checkpoint.

During meiosis, the budding yeast polo-like kinase Cdc5 is a crucial driver of the prophase I to meiosis I (G2/M) transition. The meiotic recombination checkpoint restrains cell cycle progression in response to defective recombination to ensure proper distribution of intact chromosomes to the gametes. This checkpoint detects unrepaired DSBs and ...
initiates a signaling cascade that ultimately inhibits Ndt80, a transcription factor required for CDC5 gene expression. Previous work revealed that overexpression of CDC5 partially alleviates the checkpoint-imposed meiotic delay in the synaptonemal complex-defective zip1? mutant. Here, we show that overproduction of a Cdc5 version (Cdc5-?N70), lacking the N-terminal region required for targeted degradation of the protein by the APC/C complex, fails to relieve the zip1?-induced meiotic delay, despite being more stable and reaching increased protein levels. However, precise mutation of the consensus motifs for APC/C recognition (D-boxes and KEN) has no effect on Cdc5 stability or function during meiosis. Compared to the zip1? single mutant, the zip1? cdc5-?N70 double mutant exhibits an exacerbated meiotic block and reduced levels of Ndt80 consistent with persistent checkpoint activity. Finally, using a CDC5-inducible system, we demonstrate that the N-terminal region of Cdc5 is essential for its checkpoint erasing function. Thus, our results unveil an additional layer of regulation of polo-like kinase function in meiotic cell cycle control.
Mesh Terms:
Cell Cycle Checkpoints, Cell Cycle Proteins, Down-Regulation, Meiosis, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Cells
Date: Sep. 27, 2021
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