Identification of a mutant DNA polymerase delta in Saccharomyces cerevisiae with an antimutator phenotype for frameshift mutations.

Genetics
M I HadjimarcouLinda J Reha-Krantz

Abstract

We propose that a beta-turn-beta structure, which plays a critical role in exonucleolytic proofreading in the bacteriophage T4 DNA polymerase, is also present in the Saccharomyces cerevisiae DNA pol delta. Site-directed mutagenesis was used to test this proposal by introducing a mutation into the yeast POL3 gene in the region that encodes the putative beta-turn-beta structure. The mutant DNA pol delta has a serine substitution in place of glycine at position 447. DNA replication fidelity of the G447S-DNA pol delta was determined in vivo by using reversion and forward assays. An antimutator phenotype for frameshift mutations in short homopolymeric tracts was observed for the G447S-DNA pol delta in the absence of postreplication mismatch repair, which was produced by inactivation of the MSH2 gene. Because the G447S substitution reduced frameshift but not base substitution mutagenesis, some aspect of DNA polymerase proofreading appears to contribute to production of frameshifts. Possible roles of DNA polymerase proofreading in frameshift mutagenesis are discussed.

References

Nov 3, 1975·Molecular & General Genetics : MGG·L S Ripley
Jan 25, 1992·Nucleic Acids Research·C Schlötterer, D Tautz
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·T Tsurimoto, B Stillman
Jan 1, 1989·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T S WangD Korn
Jul 25, 1986·Nucleic Acids Research·D S McPheetersL Gold
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel
Jul 1, 1970·Proceedings of the National Academy of Sciences of the United States of America·J W Drake, E O Greening
Jan 1, 1983·Methods in Enzymology·R J Rothstein
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·M StrandT D Petes
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·T A KunkelK A Johnson
Jan 5, 1993·Journal of Molecular Biology·J W Drake
Feb 25, 1993·Nucleic Acids Research·D K Braithwaite, J Ito
Feb 15, 1996·Genes & Development·G T MarsischkyR Kolodner
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·R P Baker, L J Reha-Krantz
Apr 30, 1998·Genetics·N G Nossal
May 26, 1998·Journal of Molecular Biology·L C KroutilS J Benkovic
Oct 6, 1998·Annual Review of Biochemistry·S Waga, B Stillman
Mar 19, 1999·Molecular and Cellular Biology·P V Shcherbakova, T A Kunkel
Jun 17, 1999·Journal of Molecular Biology·S FujiiH Maki
Aug 24, 1999·The Journal of Biological Chemistry·E ElisseevaL J Reha-Krantz
Nov 5, 1999·Structure·Y ZhaoJ Kuriyan
Aug 5, 2000·The Journal of Biological Chemistry·E F da Silva, L J Reha-Krantz
Dec 1, 1949·Journal of Genetics·D E LEA, C A COULSON

❮ Previous
Next ❯

Citations

Aug 28, 2007·Genetics·Michael M DesaiMarcus W Feldman
Feb 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·Natasha P DegtyarevaThomas D Petes
May 16, 2006·Genome Génome / Conseil National De Recherches Canada·Kelly MurphyLinda J Reha-Krantz
Sep 19, 2001·Yeast
Mar 11, 2003·Microbiology and Molecular Biology Reviews : MMBR·Eric S MillerWolfgang Rüger
Jun 24, 2009·Biochimica Et Biophysica Acta·Linda J Reha-Krantz

❮ 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.