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

## TL;DR

This study examines a cancer-related mutation in the NUF2 protein using yeast to understand its impact on cell division and cancer.

## Contribution

The study uses a yeast model to investigate a human cancer-associated mutation in the NUF2 protein.

## Key findings

- The nuf2 Q21A mutation in yeast does not cause growth defects or disrupt kinetochore composition.
- The mutation does not affect interactions with the Dam1 complex or Mps1 kinase.
- The results suggest the human HsNUF2 R19H mutation's role in cancer needs further investigation in human cells.

## Abstract

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.