Linked Life Data

11698339

Source:http://linkedlifedata.com/resource/pubmed/id/11698339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-11-7
pubmed:abstractText
DNA mismatch repair (MMR) corrects DNA polymerase insertion errors that have escaped proofreading in order to avoid the accumulation of deleterious mutations. While the role of MMR in the correction of replication errors is well established, its involvement in the processing of DNA damage induced by chemical and physical agents is less clear. A role for some of the MMR proteins, such as MSH2, in the repair of double strand break (DSBs) through recombination has also been envisaged. Why MMR- deficient cells are sensitive to agents causing replication fork stalling and thus DSBs remains unclear. To verify a possible role of MSH2 in homologous recombinational repair, we have treated cells from knockout mice for the MSH2 gene and mouse colorectal carcinoma cells also defective for MSH2 with different doses of camptothecin, an agent known to interfere with DNA replication. In the absence of MSH2, we found a reduced survival rate accompanied by higher levels of chromosomal damage and SCE induction. Furthermore, MSH2(-/-) cells displayed an elevated spontaneous RAD51 focus-forming activity and a higher induction of RAD51 foci following camptothecin treatment. Thus, the absence of MSH2 could result in both spontaneous DNA damage and uncontrolled recombination events leading to the observed higher yield of chromosomal damage and the higher induction of RAD51 foci following CPT treatment. Therefore, our results suggest an involvement of MSH2 in the early events leading to correct RAD51 relocalization after the formation of DSBs specifically produced at the blocked replication fork.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1781-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11698339-Animals, pubmed-meshheading:11698339-Antineoplastic Agents, Phytogenic, pubmed-meshheading:11698339-Base Pair Mismatch, pubmed-meshheading:11698339-Camptothecin, pubmed-meshheading:11698339-Cell Cycle, pubmed-meshheading:11698339-Cell Survival, pubmed-meshheading:11698339-Chromosome Aberrations, pubmed-meshheading:11698339-Colorectal Neoplasms, pubmed-meshheading:11698339-DNA Damage, pubmed-meshheading:11698339-DNA Repair, pubmed-meshheading:11698339-DNA Replication, pubmed-meshheading:11698339-DNA-Binding Proteins, pubmed-meshheading:11698339-Drug Hypersensitivity, pubmed-meshheading:11698339-Flow Cytometry, pubmed-meshheading:11698339-Mice, pubmed-meshheading:11698339-Mice, Knockout, pubmed-meshheading:11698339-MutS Homolog 2 Protein, pubmed-meshheading:11698339-Proto-Oncogene Proteins, pubmed-meshheading:11698339-Rad51 Recombinase, pubmed-meshheading:11698339-Sister Chromatid Exchange, pubmed-meshheading:11698339-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Hypersensitivity to camptothecin in MSH2 deficient cells is correlated with a role for MSH2 protein in recombinational repair.
pubmed:affiliation
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università degli Studi della Tuscia, Via S.Camillo de Lellis, 01100 Viterbo, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't