The faithful duplication and segregation of chromosomes during cell division is essential for life in all eukaryotes. Each chromosome is made up of two sister chromatids, which are held together after DNA is replicated. In humans errors during chromosome segregation can lead to miscarriages, birth defects and proliferative diseases, such as cancer.
During mitosis each sister chromatid is bound to microtubules via a multi-protein structure, known as the kinetochore. In order that sister chromatids are separated to opposite spindle poles, each kinetochore must be bound to microtubule(s) from one spindle pole and its sister kinetochore to microtubule(s) from the opposite spindle pole, a process known as chromosome bi-orientation. This process is monitored by a surveillance system, known as the spindle assembly checkpoint (SAC), which ensures sister chromatids do not separate until all chromosomes are correctly attached to microtubules and under tension.
Our research is aimed at understanding how mechanical force at the kinetochore is transmitted into a biochemical signal that silences the SAC to trigger accurate segregation of sister chromatids and how this process is subverted in various human pathologies, such as cancer.
Silió, V., McAinsh, A.D, Millar, JB. (2015) KNL1-Bubs and RZZ Provide Two Separable Pathways for Checkpoint Activation at Human Kinetochores DOI: 10.1016/j.devcel.2015.11.012. Volume 35, Issue 5, 7 December 2015, Pages 600-613 Developmental Cell
Meadows, J.C., Millar, J.B. (2015) Sharpening the anaphase switch Biochem Soc Trans, 43(1):19-22. doi: 10.1042/BST20140250. PubMed
Sarkar, S., Dalgaard, J.Z., Millar, J.B.A., Arumugam, P. (2014) The Rim15-endosulfine-PP2ACdc55 signalling module regulates entry into gametogenesis and quiescence via distinct mechanisms in budding yeast. PloS Genet. 10(6):e1004456 PubMed
Messin, L. and Millar J.B.A. (2014) Role and regulation of kinesin-8 motors through the cell cycle. Systems and Synthetic Biology 8, 205–213 PubMed
Mora-Santos, M. and Millar, J.B. (2013) Checkpoint proteins come under scrutiny. eLife 2013;2:e01494. DOI: 10.7554/eLife.01494
Sarkar, S., Shenoy, R.T., Dalgaard, J.Z., Newnham, L., Hoffmann, E., Millar, J.B. and Arumugam, P. (2013) Monopolin subunit Csm1 associates with MIND complex to establish monopolar attachment of sister kinetochores at meiosis I. PLOS. Genetics (in press)
Meadows, J.C. and Millar, J.B. (2013) Cell Biology: Polar expeditions for PP1. Curr Biol. 23:R120-2 PubMed
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