DNA repair in aging rat neurons.
This laboratory, using post-mitotic rat brain neurons as a model system, has been testing the hypothesis that the inherited DNA repair potential would have profound influence on the aging process of the individual. It has been found that both single and double strand breaks in DNA accumulate in neurons with age. Since base excision repair (BER) is the pathway to effect repair of the type of DNA damage that is likely to occur in neurons, model oligo duplexes were used to assess the BER pathway. Both extension of a primer and one or four nucleotide gap repair are markedly reduced in aging neurons as compared with the young. The extension activity could be restored by supplementing the neuronal extracts with pure DNA polymerase beta (pol beta) while the restoration of gap repair needed the addition of both pol beta and DNA ligase. It thus appears that both pol beta and DNA ligase are deficient in aging neurons. We have also established a system to study the non-homologous end joining (NHEJ) mode of DNA repair in neurons. The end joining of cohesive but not of blunt or non-matching ends, is reduced with age and attempts to identify the limiting factor(s) in this case have been unsuccessful so far. These results are reviewed vis-à-vis the existing literature.
Rao
K Subba
KS
ICMR Advanced Center for Research on Aging and Brain, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, Andhra Pradesh 500 046, India. ksrsl@uohyd.ernet.in
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency; D019951:DNA Polymerase beta / Q000172:deficiency; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000378:metabolism
D019951:DNA Polymerase beta; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP