Open AccessDeficiency in SNM1 Abolishes an Early Mitotic Checkpoint Induced by Spindle Stress
Author(s) -
Shamima Akhter,
Christopher T. Richie,
Jian Min Deng,
Eric M. Brey,
Xiaoshan Zhang,
C. Patrick,
Richard R. Behringer,
Randy J. Legerski
Publication year - 2004
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.24.23.10448-10455.2004
Subject(s) - spindle checkpoint , biology , mitotic exit , anaphase , microbiology and biotechnology , mitosis , spindle apparatus , g2 m dna damage checkpoint , cell cycle checkpoint , premature chromosome condensation , multipolar spindles , metaphase , chromosome segregation , centrosome , cell cycle , genetics , cell division , chromosome , apoptosis , cell , gene
Spindle poisons represent an important class of anticancer drugs that act by interfering with microtubule polymerization and dynamics and thereby induce mitotic checkpoints and apoptosis. Here we show that mammalian SNM1 functions in an early mitotic stress checkpoint that is distinct from the well-characterized spindle checkpoint that regulates the metaphase-to-anaphase transition. Specifically, we found that compared to wild-type cells, Snm1-deficient mouse embryonic fibroblasts exposed to spindle poisons exhibited elevated levels of micronucleus formation, decreased mitotic delay, a failure to arrest in mitosis prior to chromosome condensation, supernumerary centrosomes, and decreased viability. In addition, we show that both Snm1 and 53BP1, previously shown to interact, coimmunoprecipitate with components of the anaphase-promoting complex (APC)/cyclosome. These findings suggest that Snm1 is a component of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation.