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- Principal area
- Reproduction, mother and youth health
- 2705, boulevard Laurier, T-2-52
CANADA G1V 4G2
- +1 418-525-4444, extension 46252
- +1 418-654-2753
Aneuploidy is a pathological state defined by a chromosome number per cell that deviates from the normal for this organism. It occurs as a result of aberrant cell division, is the most prevalent genetic anomaly in man. Aneuploidy is the primary recognized cause of miscarriage, is connected to mental retardation in newborns. In adults, aneuploidy is a hallmark of almost all cancers and promotes tumor progression.
Our lab is interested in defining and understanding the signalling pathways and molecular mechanisms that ensure accurate cell division, and thus prevention of aneuploidy. In particular, we are interested in a small group of highly conserved kinases known as the “Spinde Assembly Checkpoint” or “SAC” kinases that collectively ensure an accurate cell division by two distinct mechanisms: 1) by ensuring accurate attachment of chromosome to the cell division apparatus 2) by delaying the division process until these accurate attachments are achieved.
Our research focuses on the following questions:
1. What are the mechanisms of SAC kinase activation?
2. What are the relevant substrates of the SAC kinases?
3. Is the SAC differentially regulated in chromosomally stable and chromosomally instable cell lines?
We are using interdisciplinary approaches to understand both the upstream and downstream signaling events mediated by these enzymes, including mass spectrometry, high resolution microscopy, and live-cell imaging.
Active research project(s)
Recent publications (see all publication from this researcher)
Rojas AM, Santamaria A, Malik R, Jensen TS, Korner R, Morilla I, de Juan D, Krallinger M, Hansen DA, Hoffmann R, Lees J, Reid A, Yeats C, Wehner A, Elowe S, Clegg AB, Brunak S, Nigg EA, Orengo C, Valencia A, Ranea JA. Uncovering the molecular machinery of the human spindle-an integration of wet and dry systems biology. PLoS ONE, 2012. 7: e31813
Lee S, Thebault P, Freschi L, Beaufils S, Blundell TL, Landry CR, Bolanos-Garcia VM, Elowe S. Characterization of Spindle Checkpoint Kinase Mps1 Reveals Domain with Functional and Structural Similarities to Tetratricopeptide Repeat Motifs of Bub1 and BubR1 Checkpoint Kinases. The Journal of biological chemistry, 2012. 287: 5988-6001
Thebault P, Chirgadze DY, Dou Z, Blundell TL, Elowe S, Bolanos-Garcia VM. Structural and functional insights into the role of the N-terminal Mps1 TPR domain in the SAC (spindle assembly checkpoint). The Biochemical journal, 2012. 448: 321-8
Dou Z, von Schubert C, Korner R, Santamaria A, Elowe S, Nigg EA. Quantitative mass spectrometry analysis reveals similar substrate consensus motif for human Mps1 kinase and Plk1. PLoS ONE, 2011. 6: e18793
Elowe S. Bub1 and BubR1: at the Interface between Chromosome Attachment and the Spindle Checkpoint. Molecular and cellular biology, 2011. 31: 3085-93
Santamaria A, Wang B, Elowe S, Malik R, Zhang F, Bauer M, Schmidt A, Sillje HH, Korner R, Nigg EA. The Plk1-dependent phosphoproteome of the early mitotic spindle. Molecular & cellular proteomics : MCP, 2011. 10: M110.004457
Elowe S, Dulla K, Uldschmid A, Li X, Dou Z, Nigg EA. Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1. Journal of cell science, 2010. 123: 84-94