Autor(es):
Pereira, Ana L. 
; Pereira, António J. ; Maia, Ana R.R. ; Drabek, Ksenija ; Sayas, C. Laura ; Hergert, Polla J. ; Lince-Faria, Mariana ; Matos, Irina ; Duque, Cristina ; Stepanova, Tatiana ; Rieder, Conly L. ; Earnshaw, William C. ; Galjart, Niels ; Maiato, Helder
Data: 2006
Identificador Persistente: http://hdl.handle.net/10216/35046
Origem: Repositório Aberto da Universidade do Porto
Descrição
CLASPs are widely conserved microtubule plus-end–tracking proteins with essential roles in the local regulation of
microtubule dynamics. In yeast, Drosophila, and Xenopus, a single CLASP orthologue is present, which is required for
mitotic spindle assembly by regulating microtubule dynamics at the kinetochore. In mammals, however, only CLASP1
has been directly implicated in cell division, despite the existence of a second paralogue, CLASP2, whose mitotic roles
remain unknown. Here, we show that CLASP2 localization at kinetochores, centrosomes, and spindle throughout mitosis
is remarkably similar to CLASP1, both showing fast microtubule-independent turnover rates. Strikingly, primary
fibroblasts from Clasp2 knockout mice show numerous spindle and chromosome segregation defects that can be partially
rescued by ectopic expression of Clasp1 or Clasp2. Moreover, chromosome segregation rates during anaphase A and B are
slower in Clasp2 knockout cells, which is consistent with a role of CLASP2 in the regulation of kinetochore and spindle
function. Noteworthy, cell viability/proliferation and spindle checkpoint function were not impaired in Clasp2 knockout
cells, but the fidelity of mitosis was strongly compromised, leading to severe chromosomal instability in adult cells.
Together, our data support that the partial redundancy of CLASPs during mitosis acts as a possible mechanism to prevent
aneuploidy in mammals.
