UC Santa Cruz

Accurate chromosome segregation in meiosis and mitosis is essential for avoiding aneuploidy, a hallmark of cancer cells. In meiosis, proper chromosome segregation relies upon the events of meiotic prophase: pairing, synapsis, and recombination between homologous chromosomes. After meiotic recombination, chromosome architecture must be remodeled to form bivalents, the structures that promote proper homolog portioning at meiosis I. How recombination is coupled to chromosome remodeling remains unclear. Here, we show that the conserved ZHP-3 protein, required for crossover formation, has ubiquitin ligase activity in vitro, indicating it may serve to coordinate meiotic recombination with changes in chromosome architecture. Furthermore, we identify ZHP-3 as a substrate of both the MPK-1 (MAP) and CHK-1 kinases in vitro. MAP kinase integrates developmental processes with meiotic chromosome dynamics—it may phosphorylate ZHP-3 to coordinate and regulate these events. Finally, in mitosis, the spindle checkpoint regulates the fidelity of mitotic segregation by delaying the onset of anaphase until all chromosomes are properly attached to the mitotic spindle. Here, we identify PCH-2Trip13 as a novel component of the spindle checkpoint in C. elegans. We show that through the CMT-1p31comet protein, PCH-2Trip13 regulates the amount of Mad2 that localizes to mitotic chromosomes, suggesting that PCH-2Trip13 may regulate the strength or robustness of the spindle checkpoint response. Furthermore, we show that the requirement for PCH-2Trip13 in MAD-2 recruitment to kinetochores is conserved in human epithelial RPE1 cells. Together, these data help to elucidate the mechanisms by which multiple cell types ensure proper chromosome segregation in both