title: Rev7/Mad2B plays a critical role in the assembly of a functional mitotic spindle.
abstract: The spindle assembly checkpoint (SAC) acts as a guardian against cellular threats that may lead to chromosomal missegregation and aneuploidy. Mad2, an anaphase-promoting complex/cyclosome-Cdc20 (APC/C(Cdc20)) inhibitor, has an additional homolog in mammals known as Mad2B, Mad2L2 or Rev7. Apart from its role in Polζ-mediated translesion DNA synthesis and double-strand break repair, Rev7 is also believed to inhibit APC/C by negatively regulating Cdh1. Here we report yet another function of Rev7 in cultured human cells. Rev7, as predicted earlier, is involved in the formation of a functional spindle and maintenance of chromosome segregation. In the absence of Rev7, cells tend to arrest in G2/M-phase and display increased monoastral and abnormal spindles with misaligned chromosomes. Furthermore, Rev7-depleted cells show Mad2 localization at the kinetochores of metaphase cells, an indicator of activated SAC, coupled with increased levels of Cyclin B1, an APC(Cdc20) substrate. Surprisingly unlike Mad2, depletion of Rev7 in several cultured human cell lines did not compromise SAC activity. Our data therefore suggest that besides its role in APC/C(Cdh1) inhibition, Rev7 is also required for mitotic spindle organization and faithful chromosome segregation most probably through its physical interaction with RAN.
authors.affiliation: a Department of Microbiology and Immunology ; University of Saskatchewan ; Saskatchewan , Canada.
authors.forename: Audesh
authors.initials: A
authors.lastname: Bhat
authors.affiliation: a Department of Microbiology and Immunology ; University of Saskatchewan ; Saskatchewan , Canada.
authors.forename: Zhaojia
authors.initials: Z
authors.lastname: Wu
authors.affiliation: b Carcinogenesis Laboratory; Michigan State University ; East Lansing , MI USA.
authors.forename: Veronica M
authors.initials: VM
authors.lastname: Maher
authors.affiliation: b Carcinogenesis Laboratory; Michigan State University ; East Lansing , MI USA.
authors.forename: J Justin
authors.initials: JJ
authors.lastname: McCormick
authors.affiliation: a Department of Microbiology and Immunology ; University of Saskatchewan ; Saskatchewan , Canada.|c College of Life Sciences; Capital Normal University ; Beijing , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism; D000782:Aneuploidy; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D064246:Mad2 Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*
chemical_list: C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D064173:Anaphase-Promoting Complex-Cyclosome
keywords: Mad2; RAN; Rev7/Mad2B; aneuploidy; mitosis; spindle assembly checkpoint