Release of normal bases from intact DNA by a native DNA repair enzyme

The EMBO Journal
K G BerdalE Seeberg

Abstract

Base excision repair is initiated by DNA glycosylases removing inappropriate bases from DNA. One group of these enzymes, comprising 3-methyladenine DNA glycosylase II (AlkA) from Escherichia coli and related enzymes from other organisms, has been found to have an unusual broad specificity towards quite different base structures. We tested whether such enzymes might also be capable of removing normal base residues from DNA. The native enzymes from E.coli, Saccharomyces cerevisiae and human cells promoted release of intact guanines with significant frequencies, and further analysis of AlkA showed that all the normal bases can be removed. Transformation of E. coli with plasmids expressing different levels of AlkA produced an increased spontaneous mutation frequency correlated with the expression levels, indicating that excision of normal bases occurs at biologically significant rates. We propose that the broad specificity 3-methyladenine DNA glycosylases represent a general type of repair enzyme 'pulling' bases in DNA largely at random, without much preference for a specific structure. The specificity for release of damaged bases occurs because base structure alterations cause instability of the base-sugar bonds. Damaged bases are...Continue Reading

References

Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·C G FragaB N Ames
Jan 1, 1986·Annual Review of Genetics·L A Loeb, B D Preston
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W Xiao, L Samson
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Saparbaev, J Laval
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·Z MatijasevicD B Ludlum
Dec 11, 1993·Nucleic Acids Research·T R O'Connor
Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·M K DosanjhB Singer
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T BesshoS Mitra
Oct 1, 1995·Trends in Biochemical Sciences·E SeebergM Bjørås
Apr 19, 1996·The Journal of Biological Chemistry·G FrosinaE Dogliotti

❮ Previous
Next ❯

Citations

Aug 10, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·M D WyattL D Samson
Mar 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J Ninio
Feb 27, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·O D Schärer, J Jiricny
May 21, 2013·Archives of Toxicology·Amaya Azqueta, Andrew R Collins
Jun 9, 2005·Mutation Research·Dmitry O Zharkov, Arthur P Grollman
Jun 9, 2005·Mutation Research·Joy L HuffmanJohn A Tainer
Jun 18, 2003·Biochemical and Biophysical Research Communications·Robert T ElderYuqi Zhao
Aug 1, 2000·Mutation Research·A Memisoglu, L Samson
Aug 1, 1998·Mutation Research·B J GlassnerL D Samson
Aug 1, 1998·Mutation Research·D A Gordenin, M A Resnick
Feb 25, 2000·Mutation Research·S R RajskiJ K Barton
Jun 12, 2002·Free Radical Biology & Medicine·Dmitry O Zharkov, Arthur P Grollman
Feb 3, 2000·Free Radical Biology & Medicine·M A GraziewiczB Tudek
Oct 9, 2008·Biochemistry·Mark Hedglin, Patrick J O'Brien
Feb 9, 2006·Chemical Reviews·Patrick J O'Brien
Sep 21, 2006·Journal of the American Chemical Society·Matthew T BennettAlexander C Drohat
Dec 19, 2006·Chemical Research in Toxicology·Michael D Wyatt, Douglas L Pittman
Apr 12, 2000·European Journal of Biochemistry·G Frosina
Jun 16, 2010·The Journal of Biological Chemistry·Derek M Lyons, Patrick J O'Brien
Apr 19, 2012·The Journal of Biological Chemistry·Charisse M CrenshawGregory L Verdine
Dec 23, 2004·Nucleic Acids Research·Regula Muheim-LenzHanspeter Naegeli
Oct 31, 2003·Molecular and Cellular Biology·Marie Guillet, Serge Boiteux
Jun 11, 2004·Annual Review of Biochemistry·Aziz SancarStuart Linn
Jul 20, 1999·Annual Review of Biophysics and Biomolecular Structure·C D MolJ A Tainer
Sep 24, 2010·PLoS Genetics·Jacques Ninio
Feb 19, 2000·Biochemical and Biophysical Research Communications·D PlochockaP Zielenkiewicz
Dec 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·A Y LauT Ellenberger
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·B J GlassnerL D Samson
Sep 3, 2014·Organic & Biomolecular Chemistry·Alexander C Drohat, Atanu Maiti
Aug 30, 2008·Critical Reviews in Biochemistry and Molecular Biology·Joke Baute, Anne Depicker

❮ 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.