Half-Intercalation Stabilizes Slipped Mispairing and Explains Genome Vulnerability to Frameshift Mutagenesis by Endogenous "Molecular Bookmarks"

BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology
Andrei Kuzminov

Abstract

Some 60 years ago chemicals that intercalate between base pairs of duplex DNA were found to amplify frameshift mutagenesis. Surprisingly, the robust induction of frameshifts by intercalators still lacks a mechanistic model, leaving this classic phenomenon annoyingly intractable. A promising idea of asymmetric half-intercalation-stabilizing frameshift intermediates during DNA synthesis has never been developed into a model. Instead, researchers of frameshift mutagenesis embraced the powerful slipped-mispairing concept that unexpectedly struggled with the role of intercalators in frameshifting. It is proposed that the slipped mispairing and the half-intercalation ideas are two sides of the same coin. Further, existing findings are reviewed to test predictions of the combined "half-intercalation into the slipped-mispairing intermediate" model against accumulated knowledge. The existence of potential endogenous intercalators and the phenomenon of "DNA bookmarks" reveal ample possibilities for natural frameshift mutagenisis in the cell. From this alarming perspective, it is discussed how the cell could prevent genome deterioration from frameshift mutagenesis.

References

Jan 1, 1979·Progress in Medicinal Chemistry·S Neidle
Jan 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·T D SakoreH M Sobell
Jan 1, 1978·Chemico-biological Interactions·P LecointeC Paoletti
Dec 2, 1977·Biochimica Et Biophysica Acta·R Böhner, U Hagen
Dec 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·J McCannB N Ames
Sep 1, 1991·Mutation Research·L R Ferguson, W A Denny
Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K Bebenek, T A Kunkel
Jan 5, 1990·Journal of Molecular Biology·G G Revich, L S Ripley
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·S Canning, T P Dryja
Nov 10, 1988·Biochimica Et Biophysica Acta·T A Kunkel, K Bebenek
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·C DohetM Radman
Jan 1, 1987·Annual Review of Genetics·G R Smith
Aug 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·B N AmesF D Lee
Jan 1, 1974·Annual Review of Genetics·J R Roth
Oct 15, 1974·Journal of Molecular Biology·T Kohno, J R Roth
Jan 1, 1966·Cold Spring Harbor Symposia on Quantitative Biology·M H Malamy
Aug 29, 1972·Biochemistry·E J GabbayC S Baxter
Nov 11, 1971·European Journal of Biochemistry·M Dourlent, C Hélène
Aug 1, 1969·Proceedings of the National Academy of Sciences of the United States of America·A Sarabhai, H Lamfrom
Feb 14, 1969·Journal of Molecular Biology·H J Li, D M Crothers
Aug 8, 1970·Biochimica Et Biophysica Acta·P E Brown
Jan 1, 1981·Advances in Pharmacology and Chemotherapy·W D Wilson, R L Jones
Jan 1, 1984·Molecular & General Genetics : MGG·T R Skopek, F Hutchinson
Jan 1, 1980·CRC Critical Reviews in Biochemistry·J E Coleman, J L Oakley
Jan 1, 1981·CRC Critical Reviews in Biochemistry·C Helene, J C Maurizot
Jan 1, 1981·Annual Review of Biophysics and Bioengineering·H M Berman, P R Young
Nov 25, 1981·Journal of Molecular Biology·M P Calos, J H Miller
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C S MadsenW W Hauswirth

❮ 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.