Analysis of a cancer-associated mutation in the budding yeast Nuf2 kinetochore protein

The kinetochore is a highly conserved megadalton protein complex that ensures proper chromosome segregation via microtubule attachments. The NDC80 complex is one of the major conserved microtubule binding complexes in the kinetochore. NUF2, a protein within the NDC80 complex, has been identified as a cancer gene candidate because missense mutations, found across different tumor samples, cluster within NUF2's calponin homology domain. In this study, we examined a NUF2 cancer-associated mutation in a simple and well-studied organism, Saccharomyces cerevisiae , to elucidate its effects on cell division. We studied the budding yeast nuf2 ^Q21A mutation with the intention of extrapolating our results to the homologous cancer associated mutation in Homo sapiens NUF2 ^R19H (HsNUF2 ^R19H ). Our studies demonstrate that the nuf2 ^Q21A mutant does not exhibit any growth defects or disrupt kinetochore composition. Additionally, it does not affect the Ndc80 complex's interactions with the Dam1 complex or with the Mps1 kinase. These results indicate that the yeast nuf2 ^Q21A mutant does not cause a significant defect in kinetochore function, and that the role of HsNUF2 ^R19H in cancer will need to be further investigated by directly studying the cancer-associated mutation in human cells.