Linked Life Data

14576827

Source:http://linkedlifedata.com/resource/pubmed/id/14576827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2003-10-24
pubmed:abstractText
Dysfunction of cell-cycle checkpoints in DNA mismatch repair (MMR)-deficient cells in response to DNA damage has implications for anticancer therapy and genetic instability. We have studied the cell-cycle effects of MMR deficiency (Msh2(-/-)) in primary mouse embryonic fibroblasts (MEFs) exposed to cisplatin (10 microM x 1 h) using time-lapse microscopy. Kinetic responses of MEFs from different embryos and passage ages varied, but we report a consistent drug-induced inhibition of mitotic entry (approx. 50%). There was a loss of an early-acting (<5 h) delay in G2 to M transition in Msh2(-/-) cells, although a later-acting G2 arrest was apparently normal. This suggests that Msh2 primarily acts to delay mitotic entry of cells already in G2, that is, DNA damage incurred during G2 does not influence the cell once committed to mitotic traverse. Irrespective of Msh2 status, cisplatin treatment and the incurred DNA damage did not effect mitotic traverse or show any evidence for early (within 24 h) cell death. The results indicate that Msh2(-/-) status can result in the premature commitment to mitosis of a cell subpopulation, determined by the fraction residing in G2 at the time of damage induction. The findings suggest a new route to MMR-driven genetic instability that does not rely primarily on the integrity of the late-acting checkpoint.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7642-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Single cell tracking reveals that Msh2 is a key component of an early-acting DNA damage-activated G2 checkpoint.
pubmed:affiliation
Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't