Linked Life Data

12509224

Source:http://linkedlifedata.com/resource/pubmed/id/12509224

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-1-1
pubmed:abstractText
Oxidative damage to mitochondrial DNA (mtDNA) has been implicated as a contributing factor to the origin of many pathological processes. Among the major DNA lesions generated by oxidative stress, 8-oxoguanine (8-oxoG) has a strong mutagenic potential. The main pathway for the repair of this lesion is the base excision repair (BER) initiated by the OGG1 DNA glycosylase. In human cells alternative splicing of the hOGG1 transcript yields two forms of the protein, alpha and beta, that are localised in the nucleus and the mitochondria, respectively. We describe here a hOGG1 somatic mutation, found in a kidney cancer, that modifies the intracellular localisation of beta-hOGG1. The glycine 12 to glutamic acid substitution does not affect the enzymatic activity of the enzyme but lies in what was predicted to be a mitochondrial targeting sequence (MTS). Immunocytochemical localisation experiments show that the G12E mutant protein has diffuse cytoplasmic distribution instead of the mitochondrial localisation found for the wild-type, providing an example of a single amino acid substitution capable of disrupting a MTS. These results imply that these cancer cells are deficient in their mitochondrial 8-oxoG DNA repair activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1568-7864
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Elsevier Science B.V.
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
497-505
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1 is impaired by a somatic mutation found in kidney cancer.
pubmed:affiliation
Département de Radiobiologie et Radiopathologie, UMR217 CNRS/CEA, Commissariat à l'Energie Atomique, BP6, F-92265 Fontenay aux Roses, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't