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- W50701077 abstract "In dividing cells, centrosomes act as the primary microtubule organising centre toorchestrate mitotic spindle assembly. Bipolar spindle assembly is responsible foraccurate segregation of sister chromatids, such that each daughter cell receives anidentical copy of the genome. Changes in centrosome number can lead to a lack ofmitotic fidelity and genome instability. Chromosomes are replicated in a controlled andtimely fashion and the same is true for centrosomes so that cells enter mitosis with twocentrosomes. Further to their role in spindle assembly, centrosomes are also importantin cell cycle regulation and DNA damage checkpoint signalling. Centrosomes areparticularly important in the regulation of neuroepithelial cell division in the developingbrain: all known incidences of primary microcephaly are caused by mutations incentrosome or spindle pole proteins.Xenopus laevis Cep63 is a target of DNA damage kinase, ATM, and it’s important forthe formation of bipolar mitotic spindles (Smith et al., 2009). Therefore, Cep63 is anexciting candidate for maintenance of genome stability. Human Cep63 has beenidentified as a centrosome protein (Andersen et al., 2003), but its function wasuncharacterised. In this thesis Cep63 was shown to be a constitutive centrosome protein,which plays a role in the regulation of centriole duplication. Cep152 was identified as aCep63 interacting protein; and Cep63 and Cep152 are dependent on each other for theircentrosomal localisation. Cep152 is required for centriole duplication via recruitment ofessential duplication factors, Plk4 and CPAP, to the centrosome (Dzhindzhev et al.,2010b, Cizmecioglu et al., 2010, Hatch et al., 2010b). Furthermore, mouse embryonicfibroblasts in which the Cep63 gene is disrupted show decreased centriole numbers andsigns of genome instability. Intriguingly, preliminary analysis of mouse embryos pointsto a potential link between Cep63 deficiency and microcephaly. We propose that Cep63and Cep152 function together to ensure correct centrosomal levels of the essentialcentriole duplication factors Plk4 and CPAP." @default.
- W50701077 created "2016-06-24" @default.
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- W50701077 date "2012-02-28" @default.
- W50701077 modified "2023-09-28" @default.
- W50701077 title "Characterisation of the centrosome protein Cep63" @default.
- W50701077 hasPublicationYear "2012" @default.
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