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Spindle assembly defects leading to the formation of a monopolar mitotic apparatus
Author(s) -
Tillement Vanessa,
Remy MarieHélène,
RaynaudMessina Brigitte,
Mazzolini Laurent,
Haren Laurence,
Merdes Andreas
Publication year - 2009
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20070162
Subject(s) - centrosome , microbiology and biotechnology , biology , mitosis , microtubule , spindle pole body , microtubule nucleation , kinetochore , multipolar spindles , spindle apparatus , chromosome segregation , astral microtubules , cell division , cell , cell cycle , genetics , chromosome , gene
Mitotic spindle formation in animal cells involves microtubule nucleation from two centrosomes that are positioned at opposite sides of the nucleus. Microtubules are captured by the kinetochores and stabilized. In addition, microtubules can be nucleated independently of the centrosome and stabilized by a gradient of Ran—GTP, surrounding the mitotic chromatin. Complex regulation ensures the formation of a bipolar apparatus, involving motor proteins and controlled polymerization and depolymerization of microtubule ends. The bipolar apparatus is, in turn, responsible for faithful chromosome segregation. During recent years, a variety of experiments has indicated that defects in specific motor proteins, centrosome proteins, kinases and other proteins can induce the assembly of aberrant spindles with a monopolar morphology or with poorly separated poles. Induction of monopolar spindles may be a useful strategy for cancer therapy, since ensuing aberrant mitotic exit will usually lead to cell death. In this review, we will discuss the various underlying molecular mechanisms that may be responsible for monopolar spindle formation.