An interplay between Shugoshin and Spo13 for centromeric cohesin protection and sister kinetochore mono-orientation during meiosis I in Saccharomyces cerevisiae
Meiosis is a specialized cell division process by which haploid gametes are produced from a diploid mother cell. Reductional chromosome segregation during meiosis I (MI) is achieved by two unique and conserved events: centromeric cohesin protection (CCP) and sister kinetochore mono-orientation (SKM). In Saccharomyces cerevisiae, a meiosis-specific protein Spo13 plays a role in both these centromere-specific events. Despite genome-wide association of Spo13, we failed to detect its function in global processes such as cohesin loading, cohesion establishment and homologs pairing. While Shugoshin (Sgo1) and protein phosphatase 2A (PP2ARts1) play a central role in CCP, it is not fully understood whether Spo13 functions in the process through a Sgo1- PP2ARts1-dependent or -independent mechanism. To delineate this and to find the relative contribution of each of these proteins in CCP and SKM, we meticulously observed the sister chromatid segregation pattern in the wild type, sgo1Δ, rts1Δ and spo13Δ single mutants and in their respective double mutants. We found that Spo13 protects centromeric cohesin through a Sgo1– PP2ARts1-independent mechanism. To our surprise, we observed a hitherto unknown role of Sgo1 in SKM. Further investigation revealed that Sgo1-mediated recruitment of aurora kinase Ipl1 to the centromere facilitates monopolin loading at the kinetochore during MI. Hence, this study uncovers the role of Sgo1 in SKM and demonstartes how the regulators (Sgo1, PP2ARts1, Spo13) work in a coordinated manner to achieve faithful chromosome segregation during meiosis, the failure of which leads to aneuploidy and birth defects.
KeywordsSpo13 Meiosis Cohesin Saccharomyces cerevisiae Sgo1 Mono-orientation
SKG lab is supported by the Department of Biotechnology, the Department of Science and Technology and the Board of Research in Nuclear Sciences of Govt. of India (Grant Nos. BT/PR13962/BRB/10/798/2010, SR/SO/BB-57/2009 and 37(1)/14/30/2015/BRNS, respectively). GM was supported by a CSIR fellowship (20 − 6/2009(i)EU-IV/329667). GKA was supported by a DST Inspire fellowship (DST/INSPIRE Fellowship/2015/IF150117). APB was supported by SERB-national postdoctoral fellowship (DST No: PDF/2016/000937). We would like to thank Khushboo Sinha for the strain construction.
- Bhalla N, Dernberg AF (2008) Prelude to a division. Annu Rec Cell Dev Biol 24:397–424. https://doi.org/10.1146/annurev.cellbio.23.090506.123245 CrossRefGoogle Scholar
- Longtine MS et al. (1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14:953–961. https://doi.org/10.1002/(sici)1097-0061(199807)14:10<953::aid-yea293>3.0.co;2-uGoogle Scholar
- Mehta GD, Agarwal M, Ghosh SK (2014) Functional characterization of kinetochore protein, Ctf19 in meiosis I: an implication of differential impact of Ctf19 on the assembly of mitotic and meiotic kinetochores in Saccharomyces cerevisiae. Mol Microbiol 91:1179–1199. https://doi.org/10.1111/mmi.12527 CrossRefPubMedGoogle Scholar