Linked Life Data

10987303

Source:http://linkedlifedata.com/resource/pubmed/id/10987303

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2000-9-28
pubmed:abstractText
The cytotoxicity of ionizing radiation (IR) has been associated with both the p53 pathway and with DNA mismatch repair (MMR). p53 mediates cell cycle arrest and apoptosis in response to X-ray damage, whereas the MMR complex is thought to recognize damaged bases and initiate a signal transduction pathway that can include phosphorylation of p53. To determine whether p53 and MMR mediate X-ray cytotoxicity via the same pathway, mice with targeted disruptions in either the p53 gene or the MutL homologue MMR gene Pms2 were interbred and primary fibroblasts were established from the progeny with genotypes of either wild type, p53 null, Pms2 null, or double null. Cells with either p53 or Pms2 separately disrupted showed reduced levels of apoptosis after IR in comparison with wild type, but the double null cells showed even lower levels, consistent with nonoverlapping roles for p53 and PMS2 in the X-ray response. In transformed cell lines established from the primary cells at early passage, similar differences in the apoptotic response to IR were seen, and clonogenic survival assays following low dose rate IR further showed that nullizygosity for Pms2 confers increased survival on cells in both wild-type and p53 null backgrounds. These results indicate that both p53 and MMR contribute to X-ray-induced apoptosis and that the role of MMR in the cytotoxicity of IR does not depend on p53.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4889-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Ionizing radiation-induced apoptosis via separate Pms2- and p53-dependent pathways.
pubmed:affiliation
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.