Veronica Krenn

Bub1 is an essential component of the spindle assembly checkpoint (SAC), a safety mechanism required for accurate chromosome segregation. Kinetochores are protein assemblies built on the centromeres and are essential for SAC activity. During my PhD, I investigated the molecular mechanisms that control the recruitment of Bub1 to kinetochores, a key step for correct SAC functioning. Using immunoprecipitation and localization studies, I discovered that in human cells Bub1 uses two of its subdomains to interact with the kinetochore component Knl1. One, the Bub3-binding region, allows Bub1 to interact with its partner Bub3 and to bind, together with Bub3, to MELT repeats, phosphorylated sequences located on Knl1. I found that this interaction controls the recruitment process to kinetochores and is critical for SAC activity. Additionally, the TPR of Bub1 establishes a second interaction with Knl1 to enhance Bub1 association with MELT repeats. My work describes the mechanism controlling Bub1 recruitment to kinetochores and paves the way for a molecular understanding of SAC signalling.