TSC2 Happloinsufficiency Leads to a Mutator Phenotype

Faculty Opinions recommendation of Neisseria meningitidis escape from the bactericidal activity of a monoclonal antibody is mediated by phase variation of lgtG and enhanced by a mutator phenotype.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1128820.585902 ◽

2008 ◽

Author(s):

William Shafer ◽

Maira Goytia

Keyword(s):

Monoclonal Antibody ◽

Neisseria Meningitidis ◽

Bactericidal Activity ◽

Phase Variation ◽

Mutator Phenotype

Download Full-text

The Tyr-265-to-Cys mutator mutant of DNA polymerase beta induces a mutator phenotype in mouse LN12 cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.96.17.9580 ◽

1999 ◽

Vol 96 (17) ◽

pp. 9580-9585 ◽

Cited By ~ 23

Author(s):

C. A. Clairmont ◽

L. Narayanan ◽

K.-W. Sun ◽

P. M. Glazer ◽

J. B. Sweasy

Keyword(s):

Dna Polymerase ◽

Dna Polymerase Beta ◽

Mutator Phenotype ◽

Polymerase Beta

Download Full-text

Molecular cloning of the cDNA for a mutant mouse ribonucleotide reductase M1 that produces a dominant mutator phenotype in mammalian cells.

Molecular and Cellular Biology ◽

10.1128/mcb.8.7.2698 ◽

1988 ◽

Vol 8 (7) ◽

pp. 2698-2704 ◽

Cited By ~ 36

Author(s):

I W Caras ◽

D W Martin

Keyword(s):

Ribonucleotide Reductase ◽

Mammalian Cells ◽

Mutant Mouse ◽

Chinese Hamster Ovary Cells ◽

Spontaneous Mutation ◽

Single Point ◽

Chinese Hamster ◽

Fold Increase ◽

Single Point Mutation ◽

Mutator Phenotype

Mammalian ribonucleotide reductase is regulated by the binding of dATP and other nucleotide effectors to allosteric sites on subunit M1. Using mRNA from a mutant mouse T-lymphoma (S49) cell line, we have isolated a cDNA which encodes an altered, dATP feedback-resistant subunit M1. The mutant cDNA contains a single point mutation (a G-to-A transition) at codon 57, converting aspartic acid to asparagine. Proof that this mutation is responsible for the phenotype of dATP feedback resistance is provided by the following evidence. (i) The mutation was detected only in mutant S49 cells containing dATP feedback-resistant ribonucleotide reductase and not in wild-type or other mutant S49 cells. (ii) Transfection of Chinese hamster ovary cells with an expression plasmid containing the mutant M1 cDNA resulted in the production of dATP feedback-resistant ribonucleotide reductase. Transfected CHO cells expressing the mutant M1 cDNA exhibited a 15- to 25-fold increase in the frequency of spontaneous mutation to 6-thioguanine resistance, confirming that dATP feedback-resistant ribonucleotide reductase produces a mutator phenotype in mammalian cells. The availability of a cDNA which encodes dATP feedback-resistant subunit M1 thus provides a means of manipulating by transfection the frequency of spontaneous mutation in mammalian cells.

Download Full-text

Gastrointestinal cancer of the microsatellite mutator phenotype pathway

Journal of Gastroenterology ◽

10.1007/s005350200015 ◽

2002 ◽

Vol 37 (3) ◽

pp. 153-163 ◽

Cited By ~ 39

Author(s):

Hiroyuki Yamamoto ◽

Kohzoh Imai ◽

Manuel Perucho

Keyword(s):

Gastrointestinal Cancer ◽

Mutator Phenotype

Download Full-text

Disruption of the RAD52 gene alters the spectrum of spontaneous SUP4-o mutations in Saccharomyces cerevisiae.

Genetics ◽

10.1093/genetics/122.3.535 ◽

1989 ◽

Vol 122 (3) ◽

pp. 535-542 ◽

Cited By ~ 1

Author(s):

B A Kunz ◽

M G Peters ◽

S E Kohalmi ◽

J D Armstrong ◽

M Glattke ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Base Pair ◽

Type Strain ◽

Wild Type Strain ◽

Wild Type ◽

Yeast Saccharomyces Cerevisiae ◽

Mutator Phenotype ◽

In The Wild ◽

Single Base Pair ◽

Almost All

Abstract Defects in the RAD52 gene of the yeast Saccharomyces cerevisiae confer a mutator phenotype. To characterize this effect in detail, a collection of 238 spontaneous SUP4-o mutations arising in a strain having a disrupted RAD52 gene was analyzed by DNA sequencing. The resulting mutational spectrum was compared to that derived from an examination of 222 spontaneous mutations selected in a nearisogenic wild-type (RAD52) strain. This comparison revealed that the mutator phenotype was associated with an increase in the frequency of base-pair substitutions. All possible types of substitution were detected but there was a reduction in the relative fraction of A.T----G.C transitions and an increase in the proportion of G.C----C.G transversions. These changes were sufficient to cause a twofold greater preference for substitutions at G.C sites in the rad52 strain despite a decrease in the fraction of G.C----T.A transversions. There were also considerable differences between the distributions of substitutions within the SUP4-o gene. Base-pair changes occurred at fewer sites in the rad52 strain but the mutated sites included several that were not detected in the RAD52 background. Only two of the four sites that were mutated most frequently in the rad52 strain were also prominent in the wild-type strain and mutation frequencies at almost all sites common to both strains were greater for the rad52 derivative. Although single base-pair deletions occurred in the two strains with similar frequencies, several classes of mutation that were recovered in the wild-type background including multiple base-pair deletions, insertions of the yeast transposable element Ty, and more complex changes, were not detected in the rad52 strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text