Linked Life Data

15580308

Source:http://linkedlifedata.com/resource/pubmed/id/15580308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-1-20
pubmed:abstractText
An important anticarcinogenic function of the mismatch repair (MMR) system is its role in preventing recombination between similar, but nonidentical (homeologous) sequences, thus preventing chromosomal rearrangements. We recently identified a novel chromosomal instability (CIN) phenotype in an MMR defective colon cancer cell line (HCA7) characterized by an ongoing tendency to multiple reciprocal chromosomal translocations. To analyse the relation between MMR and chromosomal changes more closely, the HCA7 stem clone was divided into three stocks. The first was stably transfected with MLH1 expression plasmid, the second was regularly exposed to the demethylating agent 5-azacytidin to re-express the hypermethylated MLH1 gene, and the third was an unmanipulated control stock. All stocks were propagated in vitro for 55-80 passages and, furthermore, some of the early passages were irradiated to induce DNA double-strand breaks. Multiplex-fluorescent in situ hybridization (M-FISH) analysis showed that all three stocks acquired varying numbers of reciprocal translocations and other structural changes at some point. Interestingly, the control stock, which is MMR defective, maintained its numerical chromosomal stability, while some of the MMR-proficient clones showed additional numerical instability. Although the control stock was less sensitive to irradiation, its surviving clones showed marked stability of chromosome structure and number compared to the MMR-competent stocks. These results show that restoring MMR does not prevent the development of reciprocal translocations but rather predisposes cells to numerical CIN after irradiation. Thus, the accumulating data suggest that MMR defect may not be necessary for the development of reciprocal chromosomal translocations but might be permissive.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
706-13
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Restoring mismatch repair does not stop the formation of reciprocal translocations in the colon cancer cell line HCA7 but further destabilizes chromosome number.
pubmed:affiliation
Department of Medical Genetics, Helsinki University, Helsinki, Finland. Wael.Abdel-Rahman@helsinki.fi
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't