Paper from the Marston lab featured in Current Biology. Authors Image Kinetochores need to be specialized to direct the distinctive pattern of chromosome segregation in meiosis. Borek et al. reveal the protein composition of kinetochores in meiosis and identify a critical assembly pathway that promotes kinetochore specialization. Borek, W.E., Vincenten, N., Duro, E., Makrantoni, V., Spanos, C., Sarangapani, K.K., Flavia de Lima, A., Kelly, D.A., Asbury, C.L., Rappsilber, J., and Marston, A.L. Summary of Paper by Lori Koch The kinetochore is a large protein complex that assembles on every chromosome and connects it to dynamic microtubule fibres to ensure it will be segregated and inherited properly. During the specialised cell division of meiosis, two rounds of chromosome segregation occur without an intervening replication phase to produce gamete cells such as egg and sperm with half the genetic content. To accomplish this feat, kinetochores play unique roles such as facilitating mono-orientation of homologous chromosomes in the first round of segregation, meiosis I. In their recent publication in Current Biology, researchers in the Marston group and their colleagues led by postdoctoral scientist Weronika Borek used proteomics and live cell imaging to reveal how the kinetochore is dramatically reorganised during meiosis I and also uniquely dependent on proteins in the Ctf19CCAN subcomplex. Their strategy involved immunoprecipitation of the centromeric DNA upon which the kinetochore is assembled followed by mass spectrometry to identify the associated proteins. They used label free quantification (LFQ) to measure differences between the amounts of kinetochore and centromere proteins found in meiotic prophase, meiotic metaphase I, versus mitotically dividing cells. They then repeated this strategy in cells lacking components of the Ctf19CCAN sub-complex of the inner kinetochore. The absence of Ctf19CCAN caused only minor alterations to kinetochore composition in mitotic cells, however there was a dramatic loss of integrity of the kinetochore structure in meiosis. Using elegant live-cell imaging experiments, the scientists discovered that the disintegration of the kinetochore in the absence of Ctf19CCAN occurred very early on in meiosis. Accordingly, tracking chromosome segregation showed that significant and lethal errors occurred in meiotic but not mitotic cells lacking Ctf19CCAN proteins. Future work will determine precisely why Ctf19CCAN is essential for meiosis. Related links Journal Link Marston Lab Website DOI This article was published on 2024-06-17
