Mutators, Antimutators, and DNA Replication Errors: A Summary and Perspective

1982 ◽  
pp. 231-234
Author(s):  
Maurice J. Bessman
Keyword(s):  
Dna Replication ◽  
Replication Errors ◽  
Dna Replication Errors

scholarly journals 3′ → 5′ Exonucleases of DNA Polymerases ϵ and δ Correct Base Analog Induced DNA Replication Errors on Opposite DNA Strands in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 717-726 ◽  
Author(s):  
Polina V Shcherbakova ◽  
Youri I Pavlov
Keyword(s):  
Dna Replication ◽  
Dna Polymerases ◽  
Replication Errors ◽  
Dna Strands ◽  
Base Analog ◽  
Chromosome Iii ◽  
Dna Strand ◽  
Dna Replication Errors ◽  
Yeast Mutants ◽  
Lagging Strand

Abstract The base analog 6-N-hydroxylaminopurine (HAP) induces bidirectional GC → AT and AT → GC transitions that are enhanced in DNA polymerase ϵ and δ 3′ → 5′ exonuclease-deficient yeast mutants, pol2-4 and pol3-01, respectively. We have constructed a set of isogenic strains to determine whether the DNA polymerases δ and ϵ contribute equally to proofreading of replication errors provoked by HAP during leading and lagging strand DNA synthesis. Site-specific GC → AT and AT → GC transitions in a Pol→, pol2-4 or pol3-01 genetic background were scored as reversions of ura3 missense alleles. At each site, reversion was increased in only one proofreading-deficient mutant, either pol2-4 or pol3-01, depending on the DNA strand in which HAP incorporation presumably occurred. Measurement of the HAP-induced reversion frequency of the ura3 alleles placed into chromosome III near to the defined active replication origin ARS306 in two orientations indicated that DNA polymerases ϵ and δ correct HAP-induced DNA replication errors on opposite DNA strands.

scholarly journals Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors

1997 ◽  
Vol 74 (3) ◽  
pp. 330-334 ◽  
Author(s):  
Rafael Rosell ◽  
Alex Pifarré ◽  
Mariano Monzó ◽  
Julio Astudillo ◽  
M. Paz López-Cabrerizo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Replication ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Replication Errors ◽  
Dna Replication Errors

scholarly journals Pathway correcting DNA replication errors in Saccharomyces cerevisiae.

1993 ◽  
Vol 12 (4) ◽  
pp. 1467-1473 ◽  
Author(s):  
A. Morrison ◽  
A.L. Johnson ◽  
L.H. Johnston ◽  
A. Sugino
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Replication ◽  
Replication Errors ◽  
Dna Replication Errors

scholarly journals Spontaneous mutation in Escherichia coli containing the dnaE911 DNA polymerase antimutator allele.

Genetics ◽  
1994 ◽  
Vol 138 (2) ◽  
pp. 263-270 ◽  
Author(s):  
A R Oller ◽  
R M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Mismatch Repair ◽  
Dna Polymerase ◽  
Spontaneous Mutation ◽  
Gene Encoding ◽  
Replication Errors ◽  
Lac Operator ◽  
Laci Gene ◽  
Dna Replication Errors

Abstract We have previously isolated mutants of Escherichia coli that replicate their DNA with increased fidelity. These mutants have a mutation in the dnaE gene, encoding the alpha subunit of DNA polymerase III. They were isolated in a mismatch-repair-defective mutL background, in which mutations can be considered to represent uncorrected DNA replication errors. In the present study we analyze the effect of one of these alleles, dnaE911, on spontaneous mutagenesis in a mismatch-repair-proficient background. In this background, spontaneous mutations may be the sum of uncorrected replication errors and mutations resulting from other pathways. Hence, the effect of the dnaE allele may provide insights into the contribution of uncorrected DNA replication errors to spontaneous mutation. The data show that dnaE911 decreases the level of Rifr, lacI and galK mutations in this background by 1.5-2-fold. DNA sequencing of 748 forward mutants in the lacI gene reveals that this effect has a clear specificity. Transversions are decreased by approximately 3-fold, whereas transitions, frameshifts, deletions and duplications remain essentially unchanged. Among the transversions, A.T-->T.A are affected most strongly (approximately 6-fold). In addition to this effect on transversions within the lacI gene, one previously recognized A.T-->G.C base-pair substitution hotspot in the lac operator is also reduced (approximately 5-fold). The data are discussed in the light of the role of DNA replication errors in spontaneous mutation, as well as other possible explanations for the observed antimutator effects.

scholarly journals Prognostic Significance of DNA Replication Errors in Young Patients With Colorectal Cancer

1998 ◽  
Vol 227 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Jeffrey R. Lukish ◽  
Kenji Muro ◽  
John DeNobile ◽  
Rachel Katz ◽  
John Williams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Replication ◽  
Prognostic Significance ◽  
Young Patients ◽  
Replication Errors ◽  
Dna Replication Errors

scholarly journals Immunohistochemical characteristics of colorectal carcinoma with DNA replication errors

1996 ◽  
Vol 11 (2) ◽  
pp. 137 ◽  
Author(s):  
Hoguen Kim ◽  
Jun Keun Jung ◽  
Jeon Han Park ◽  
Chanil Park
Keyword(s):  
Dna Replication ◽  
Colorectal Carcinoma ◽  
Replication Errors ◽  
Dna Replication Errors

scholarly journals Evidence for Preferential Mismatch Repair of Lagging Strand DNA Replication Errors in Yeast

2003 ◽  
Vol 13 (9) ◽  
pp. 744-748 ◽  
Author(s):  
Youri I. Pavlov ◽  
Ibrahim M. Mian ◽  
Thomas A. Kunkel
Keyword(s):  
Dna Replication ◽  
Mismatch Repair ◽  
Replication Errors ◽  
Dna Replication Errors ◽  
Lagging Strand

scholarly journals UV-exposure, endogenous DNA damage, and DNA replication errors shape the spectra of genome changes in human skin

PLoS Genetics ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. e1009302
Author(s):  
Natalie Saini ◽  
Camille K. Giacobone ◽  
Leszek J. Klimczak ◽  
Brian N. Papas ◽  
Adam B. Burkholder ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Human Skin ◽  
Somatic Mutations ◽  
Healthy Individuals ◽  
Mutation Load ◽  
Replication Errors ◽  
Skin Cells ◽  
Somatic Genome ◽  
Dna Replication Errors

Human skin is continuously exposed to environmental DNA damage leading to the accumulation of somatic mutations over the lifetime of an individual. Mutagenesis in human skin cells can be also caused by endogenous DNA damage and by DNA replication errors. The contributions of these processes to the somatic mutation load in the skin of healthy humans has so far not been accurately assessed because the low numbers of mutations from current sequencing methodologies preclude the distinction between sequencing errors and true somatic genome changes. In this work, we sequenced genomes of single cell-derived clonal lineages obtained from primary skin cells of a large cohort of healthy individuals across a wide range of ages. We report here the range of mutation load and a comprehensive view of the various somatic genome changes that accumulate in skin cells. We demonstrate that UV-induced base substitutions, insertions and deletions are prominent even in sun-shielded skin. In addition, we detect accumulation of mutations due to spontaneous deamination of methylated cytosines as well as insertions and deletions characteristic of DNA replication errors in these cells. The endogenously induced somatic mutations and indels also demonstrate a linear increase with age, while UV-induced mutation load is age-independent. Finally, we show that DNA replication stalling at common fragile sites are potent sources of gross chromosomal rearrangements in human cells. Thus, somatic mutations in skin of healthy individuals reflect the interplay of environmental and endogenous factors in facilitating genome instability and carcinogenesis.

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