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Title: Centromeres and telomeres display unanticipated and interchangeable roles in promoting nuclear division in fission yeast
Author: Fennell, A. C. G. E.
ISNI:       0000 0004 5364 9209
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Telomeres and centromeres have traditionally been considered to perform fundamentally distinct roles. A non-classical, but fundamental role of telomeres occurs in meiosis. Disruption of the fission yeast telomere bouquet (the conserved chromosomal configuration specific to meiotic prophase) causes a failure of the spindle pole body (SPB, the yeast centrosome equivalent) to accumulate the gamma-tubulin complex and nucleate spindles at the first meiotic division, resulting in defective meiotic SPB separation and spindle formation (Tomita and Cooper, 2007). Hence, the association of telomeres with the SPBs during meiotic prophase is crucial for subsequent SPB behaviour. Nonetheless, in 50% of bouquet deficient zygotes, spindles form properly. Here we show that bouquet deficient cells can successfully undergo meiosis using centromeres instead of telomeres to generate spindle formation. Moreover, forced association between centromeres and SPBs fully rescues SPB and spindle defects incurred by bouquet disruption - a rescue that is not induced to the same extent by non-centromeric regions. The rescue mediated by centromeres is independent of heterochromatin and outer kinetochore components. These observations demonstrate a shared ability of telomeres and centromeres to modify the SPB and ensure meiotic progression. Another interesting feature in those bouquet deficient cells displaying bipolar meiotic spindles is an increase in chromosome mis-segregation. With high temporal resolution the interaction between centromeres and telomeres in the early stages of meiosis was characterised in live cells and defined as the point at which the telomeres may communicate with the centromeres to ensure complete meiotic kinetochore assembly. These observations demonstrate a striking level of functional interchangeability between distinct chromosomal landmarks as well as an unprecedented level of communication between centromeres and telomeres, and between specialised chromosomal regions and the spindle assembly machinery. Experiments to determine whether the centromeres play a similar role in controlling mitotic spindle formation are also described.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available