Linked Life Data

20023427

Source:http://linkedlifedata.com/resource/pubmed/id/20023427

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-22
pubmed:abstractText
Progression into mitosis in the presence of DNA damage leads to spindle checkpoint (SAC) dependent mitotic delays and cytokinesis failure. In Drosophila embryos, DNA damage does not delay mitotic entry but triggers Checkpoint kinase-2 (Chk2) kinase dependent delays in mitotic exit. It is unclear if damage associated mitotic delays in human cells result from kinase signaling or breaks in centromere DNA that disrupt kinetochore function and activate the SAC. We show that transgenic expression of Human Chk2 in a Drosophila chk2 mutant background restores damage induced mitotic delays during early embryogenesis. Parental HCT116 colorectal cancer cells that progress into mitosis following DNA damage, due to either G(2) checkpoint adaptation or G(2) checkpoint abrogation by caffeine or the Chk1 inhibitor UCN-01, delay in mitosis and show high rates of cytokinesis failure. Significantly, these mitotic responses are suppressed in HCT116 chk2 knockout cells, and the response is restored by transgenic expression of wild type Chk2. However, both parental and chk2(-/-)HCT116 cells arrested in G(2) for prolonged periods by DNA damage prior to release from the G(2) block do show significant mitotic delays. Chk2 thus appears to have a conserved function in control of mitotic progression following G(2)/M transition with DNA damage. However, prolonged G(2) arrest with DNA damage can trigger Chk2 independent mitotic delays that may be secondary to kinetochore disruption.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
312-20
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A role for Chk2 in DNA damage induced mitotic delays in human colorectal cancer cells.
pubmed:affiliation
Program in Cell and Developmental Dynamics, University of Massachusetts Medical School, Worcester, MA, USA. Hanne.Varmark@umassmed.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural