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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-1-17
pubmed:abstractText
A close relationship between the DNA repair potential of various organisms and their rate of aging has been long suspected. We have been looking into the steps of the DNA repair process in isolated neurons from rats of different ages. Unscheduled DNA synthesis (UDS) was low in aging neurons, and also the response of these cells to raise their DNA repair capacity against a mutagenic challenge was poor. Attempts to identify the possible defective locus in the overall DNA repair pathways indicated that the step involving DNA polymerase may be defective. The activity of DNA polymerase-beta, the most predominant DNA polymerase in neurons that is generally considered to be a short-patch repair enzyme, shows a significant decrease in aging neurons. Northern and Southern blotting and immunotitration experiments suggest that there may be an accumulation of inactive beta polymerase molecules in the aging rat brain. Most recent preliminary studies reveal significant 3'-5' exonuclease activity in rat neurons at all ages. However, extension of a primer in a synthetic oligo duplex, either with a mismatch or correct base pair at the 3' end of the primer, was low in neurons of any age and was very poor (almost undetectable) in older ones. Supplementation of neuronal extracts with pure polymerase enzyme revealed that only polymerase beta, but not polymerase alpha, was able to increase the primer extension activity significantly in old neurons. These findings are taken to indicate an age-dependent decline in the DNA repair capacity of neurons and that DNA polymerase beta is a key player in the DNA repair mechanisms of nerve cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
928
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
113-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
DNA polymerase-beta may be the main player for defective DNA repair in aging rat neurons.
pubmed:affiliation
Department of Biochemistry, School of Life Sciences, University of Hyderabad, India. ksrsl@uohyd.ernet.in
pubmed:publicationType
Journal Article, Comparative Study, Review, Research Support, Non-U.S. Gov't