Inhibition of DNA replication fork progression and mutagenic potential of 1, N6-ethenoadenine and 8-oxoguanine in human cell extracts

Nucleic Acids Research
Joel H TolentinoAshis K Basu

Abstract

Comparative mutagenesis of 1,N(6)-ethenoadenine (epsilonA) and 8-oxoguanine (8-oxoG), two endogenous DNA lesions that are also formed by exogenous DNA damaging agents, have been evaluated in HeLa and xeroderma pigmentosum variant (XPV) cell extracts. Two-dimensional gel electrophoresis of the duplex M13mp2SV vector containing these lesions established that there was significant inhibition of replication fork movement past epsilonA, whereas 8-oxoG caused only minor stalling of fork progression. In extracts of HeLa cells, epsilonA was weakly mutagenic inducing all three base substitutions in approximately equal frequency, whereas 8-oxoG was 10-fold more mutagenic inducing primarily G-->T transversions. These data suggest that 8-oxoG is a miscoding lesion that presents a minimal, if any, block to DNA replication in human cells. We hypothesized that bypass of epsilonA proceeded principally by an error-free mechanism in which the undamaged strand was used as a template, since this lesion strongly blocked fork progression. To examine this, we determined the sequence of replication products derived from templates in which a G was placed across from the epsilonA. Consistent with our hypothesis, 93% of the progeny were derived from repl...Continue Reading

References

Apr 11, 1992·Nucleic Acids Research·O Hyrien, M Méchali
Oct 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·B SingerB Rydberg
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J D Roberts, T A Kunkel
Jan 1, 1994·Drug Metabolism Reviews·H BartschY Guichard
Jul 1, 1993·Trends in Genetics : TIG·A P Grollman, M Moriya
May 23, 1997·The Journal of Biological Chemistry·M Cordeiro-StoneW K Kaufmann
Jan 1, 1997·Critical Reviews in Biochemistry and Molecular Biology·P A Bullock
May 18, 1999·The Journal of Biological Chemistry·P FortiniE Dogliotti
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·C L LimoliJ E Cleaver
May 29, 2001·The Journal of Biological Chemistry·R L LevineM Moriya
Oct 5, 2001·Molecular and Cellular Biology·L HaracskaS Prakash
Jan 31, 2002·Nature Genetics·Nada Al-TassanJeremy P Cheadle
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sharon AvkinZvi Livneh
May 29, 2002·Free Radical Biology & Medicine·Miral DizdarogluHenry Rodriguez
Nov 18, 2003·Cellular and Molecular Life Sciences : CMLS·A R Parker, J R Eshleman
Nov 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Chad A DumstorfThomas A Kunkel
Jul 7, 2007·Science·Zachary F PursellThomas A Kunkel

❮ Previous
Next ❯

Citations

Dec 20, 2008·The Journal of Biological Chemistry·Xueshan GaoJohn W Eaton
Nov 2, 2011·DNA Repair·James T MutambaBevin P Engelward
Aug 29, 2014·Journal of Biochemical and Molecular Toxicology·Kimberly N HermanScott D McCulloch
Sep 17, 2011·Chemistry & Biodiversity·Michael P StoneGanesh Shanmugam
May 26, 2020·Critical Reviews in Biochemistry and Molecular Biology·Huidong Zhang
Mar 20, 2019·Scientific Reports·Justyna McIntyreEwa Sledziewska-Gojska
Aug 9, 2020·Malaria Journal·Nattapon PinthongPorntip Chavalitshewinkoon-Petmitr
Aug 8, 2019·DNA Repair·Jennifer KayBevin Engelward
Dec 5, 2020·Scientific Reports·Miki HanasakiHiroshi Masumoto
Jun 17, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·F Peter Guengerich, Pratibha P Ghodke
Oct 29, 2020·Chemical Research in Toxicology·Katelyn L Rioux, Sarah Delaney

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
FCS
density gradient centrifugation

Software Mentioned

ImageQuant

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.