Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-26
pubmed:abstractText
The spindle assembly checkpoint is essential to maintain genomic stability during cell division. We analyzed the role of the putative Drosophila Mad2 homologue in the spindle assembly checkpoint and mitotic progression. Depletion of Mad2 by RNAi from S2 cells shows that it is essential to prevent mitotic exit after spindle damage, demonstrating its conserved role. Mad2-depleted cells also show accelerated transit through prometaphase and premature sister chromatid separation, fail to form metaphases, and exit mitosis soon after nuclear envelope breakdown with extensive chromatin bridges that result in severe aneuploidy. Interestingly, preventing Mad2-depleted cells from exiting mitosis by a checkpoint-independent arrest allows congression of normally condensed chromosomes. More importantly, a transient mitotic arrest is sufficient for Mad2-depleted cells to exit mitosis with normal patterns of chromosome segregation, suggesting that all the associated phenotypes result from a highly accelerated exit from mitosis. Surprisingly, if Mad2-depleted cells are blocked transiently in mitosis and then released into a media containing a microtubule poison, they arrest with high levels of kinetochore-associated BubR1, properly localized cohesin complex and fail to exit mitosis revealing normal spindle assembly checkpoint activity. This behavior is specific for Mad2 because BubR1-depleted cells fail to arrest in mitosis under these experimental conditions. Taken together our results strongly suggest that Mad2 is exclusively required to delay progression through early stages of prometaphase so that cells have time to fully engage the spindle assembly checkpoint, allowing a controlled metaphase-anaphase transition and normal patterns of chromosome segregation.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-10402457, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-10436016, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-10639145, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-10973989, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-11102811, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-11483958, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-11535616, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-11702782, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-11707408, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-11726501, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12019777, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12049731, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12163471, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12360190, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12419179, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12689587, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-12855955, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-14600262, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-14990952, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15020684, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15021889, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15075237, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15182668, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15220531, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15239953, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15592459, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15615783, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15824131, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15886105, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-15933723, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-16084093, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-16199875, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-16214339, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-1651171, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-1651172, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-1660828, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-7642708, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-7642709, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-7954813, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-8384932, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-8824188, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-8978614, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-9425344, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-9606211, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-9660858, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-9786942, http://linkedlifedata.com/resource/pubmed/commentcorrection/17182852-9914370
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1059-1524
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
850-63
pubmed:dateRevised
2010-9-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Mad2-independent spindle assembly checkpoint activation and controlled metaphase-anaphase transition in Drosophila S2 cells.
pubmed:affiliation
Instituto de Biologia Molecular e Celular, 4150-180 Porto, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't