Decline of nuclear and mitochondrial oxidative base excision repair activity in late passage human diploid fibroblasts

DNA Repair
Guang-Ping ShenSusan S Wallace

Abstract

There are numerous studies documenting the increase of oxidative DNA damage in the nuclei and mitochondria of senescing cells as well as in tissues of aging animals. Here, we show that in IMR 90 human diploid fibroblasts, DNA repair activity is robust in both nuclear and mitochondrial extracts, however, the levels of activity differed against the three substrates tested. In extracts, cleavage of the 8-oxoguanine substrate, and to a lesser extent the dihydrouracil-containing substrate, occurred in a concerted reaction between the DNA glycosylases and the second enzyme in the reaction, hAPE. Cleavage of both the furan and the dihydrouracil-containing substrates was unchanged when nuclear extracts from early and late passage cells were compared. However, cleavage of the 8-oxoguanine substrate was substantially reduced in the nuclear extracts from late passage cells and significantly reduced transcription from the hOGG1 gene was observed. When mitochondrial extracts were examined, activity on all three substrates was significantly reduced, with the reduction in hAPE activity being the most marked. The reduction in cleavage of the furan substrate was not simply due to inactive mitochondrial AP endonuclease but a substantially reduce...Continue Reading

References

Sep 1, 1992·Mutation Research·C Richter
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J P PhillipsA J Hilliker
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R AdelmanB N Ames
Dec 1, 1993·Mutation Research·V Haley-Zitlin, A Richardson
Jul 1, 1995·Mutation Research·C C ShenG L Wilson
Oct 1, 1995·Mutation Research·V A Bohr, R M Anson
Sep 25, 1995·Biochemical and Biophysical Research Communications·T HiranoH Kasai
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·Q ChenB N Ames
Oct 20, 1994·Mechanisms of Ageing and Development·R S SohalH Lal
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·M K ShigenagaB N Ames
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·Q Chen, B N Ames
Jun 1, 1993·The Biochemical Journal·J R Vanfleteren
Feb 23, 1996·Cell·J Campisi
Jul 5, 1996·Science·R S Sohal, R Weindruch
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·F M Yakes, B Van Houten
Mar 1, 1997·Genes & Development·L JayaramanC Prives
Mar 6, 1998·Molecular and Cellular Biology·K G Pinz, D F Bogenhagen
Apr 30, 1998·Physiological Reviews·K B Beckman, B N Ames
May 20, 1998·Teratogenesis, Carcinogenesis, and Mutagenesis·A RedaelliG Frosina
Dec 5, 1998·Mutation Research·N DruzhynaG L Wilson
Dec 8, 1998·Journal of Neuroscience Research·M EdwardsJ R Perez-Polo
Feb 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·S MelovD C Wallace
Feb 27, 1999·Current Opinion in Structural Biology·S S ParikhJ A Tainer
Mar 17, 1999·Biochimica Et Biophysica Acta·E BonillaE A Schon
Mar 31, 1999·Free Radical Research·E K HudsonR G Hansford
Aug 12, 1999·Biochemical and Biophysical Research Communications·S Grösch, B Kaina
Sep 16, 1999·Mutation Research·D E Sawyer, B Van Houten
Dec 3, 1999·Science·T Lindahl, R D Wood
Apr 25, 2000·Archives of Biochemistry and Biophysics·S Boiteux, J P Radicella
Jul 6, 2000·FEBS Letters·H E KrokanG Slupphaug
Jul 8, 2000·The Journal of Biological Chemistry·D O ZharkovA P Grollman
Dec 21, 2000·Brain Research·B S MandavilliB Van Houten

❮ Previous
Next ❯

Citations

Jun 5, 2004·DNA Repair·Monica M McTigueCarlos R De Los Santos
May 10, 2005·DNA Repair·Bennett Van HoutenJanine H Santos
Jul 21, 2010·Mutagenesis·Megan J OsmondElizabeth T Snow
Oct 5, 2007·Nucleic Acids Research·Vera GorbunovaChristpher Hine
Nov 5, 2014·Free Radical Research·In Youb ChangSang Pil Yoon
May 20, 2008·DNA Repair·Nadja C de Souza-PintoVilhelm A Bohr
Nov 16, 2004·Mechanisms of Ageing and Development·Bartosz SzczesnyIstvan Boldogh
Sep 17, 2005·Aging Cell·Jennifer BoyleChristopher N Parris
Feb 9, 2008·Free Radical Biology & Medicine·Paula I MoreiraGeorge Perry
Jan 26, 2010·Experimental Gerontology·Ricardo GredillaTinna Stevnsner
Mar 25, 2008·DNA Repair·Dominika M Wiktor-BrownBevin P Engelward
Jun 24, 2006·Methods in Enzymology·Viswanath BandaruSusan S Wallace
Sep 17, 2004·International Journal of Radiation Biology·I R Radford
Jul 29, 2004·Clinical Science·Mikhail F AlexeyevGlenn L Wilson
Jul 30, 2005·Mitochondrion·Nicolai Balle LarsenLene Juel Rasmussen
Apr 22, 2008·Mechanisms of Ageing and Development·Guogang XuChristi A Walter

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.