Journal
NATURE
Volume 409, Issue 6818, Pages 355-359Publisher
MACMILLAN PUBLISHERS LTD
DOI: 10.1038/35053094
Keywords
-
Categories
Ask authors/readers for more resources
The mitotic checkpoint protein hsMad2 is required to arrest cells in mitosis when chromosomes are unattached to the mitotic spindle(1). The presence of a single, lagging chromosome is sufficient to activate the checkpoint, producing a delay at the metaphase-anaphase transition until the last spindle attachment is made(2). Complete loss of the mitotic checkpoint results in embryonic lethality owing to chromosome mis-segregation in various organisms(3-6). Whether partial loss of checkpoint control leads to more subtle rates of chromosome instability compatible with cell viability remains unknown. Here we report that deletion of one MAD2 allele results in a defective mitotic checkpoint in both human cancer cells and murine primary embryonic fibroblasts. Checkpoint-defective cells show premature sister-chromatid separation in the presence of spindle inhibitors and an elevated rate of chromosome mis-segregation events in the absence of these agents. Furthermore, Mad2(+/-) mice develop lung tumours at high rates after long latencies, implicating defects in the mitotic checkpoint in tumorigenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available