Haspin is an atypical protein kinase; in several organisms it phosphorylates histone H3 on Thr3 and is involved in chromosome segregation. In Saccharomyces cerevisiae, H3Thr3 phosphorylation has never been observed and the function of haspin is unknown. We report that deletion of both ALK1 and ALK2, encoding the haspin paralogs, causes the mislocalization of polarisome components. Following a transient mitotic arrest, this leads to an overly polarized actin distribution within the bud, where the mitotic spindle is consequently pulled. Here, spindle elongates generating anucleated mothers and binucleated daughters. Reducing the intensity of the bud-directed pulling forces partially restores proper cell division, suggesting that haspin controls the localization of polarity cues to preserve the coordination between polarization and the cell cycle, and to tolerate transient mitotic arrests. The evolutionary conservation of haspin and of the polarization pathways suggest that this function of haspin may be likely shared with other eukaryotic cells. We thus investigated a possible conservation of this control mechanism in mammalian cells, where indeed we found that haspin governs the orientation of the mitotic spindle thanks to its contribution to actin organization

A NEW HASPIN ROLE AT THE INTERSECTION BETWEEN MITOSIS AND CELLULAR POLARIZATION

PANIGADA, DAVIDE
2013

Abstract

Haspin is an atypical protein kinase; in several organisms it phosphorylates histone H3 on Thr3 and is involved in chromosome segregation. In Saccharomyces cerevisiae, H3Thr3 phosphorylation has never been observed and the function of haspin is unknown. We report that deletion of both ALK1 and ALK2, encoding the haspin paralogs, causes the mislocalization of polarisome components. Following a transient mitotic arrest, this leads to an overly polarized actin distribution within the bud, where the mitotic spindle is consequently pulled. Here, spindle elongates generating anucleated mothers and binucleated daughters. Reducing the intensity of the bud-directed pulling forces partially restores proper cell division, suggesting that haspin controls the localization of polarity cues to preserve the coordination between polarization and the cell cycle, and to tolerate transient mitotic arrests. The evolutionary conservation of haspin and of the polarization pathways suggest that this function of haspin may be likely shared with other eukaryotic cells. We thus investigated a possible conservation of this control mechanism in mammalian cells, where indeed we found that haspin governs the orientation of the mitotic spindle thanks to its contribution to actin organization
16-mag-2013
Inglese
Haspin ; mitosis ; polarization ; asymmetric cell division
MUZI FALCONI, MARCO
Università degli Studi di Milano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/76488
Il codice NBN di questa tesi è URN:NBN:IT:UNIMI-76488