Spectrum of Spontaneous Mutations in a CDNA of the Human Hprt Gene Integrated in Chromosomal DNA

Overview

Journal Mol Gen Genet

Specialties Genetics
Molecular Biology

Date 1989 Nov 1

PMID 2622450

Citations 10

Authors

H Ikehata

T Akagi

H Kimura

S Akasaka

T Kato

Affiliations

Soon will be listed here.

Abstract

Altered sequences were determined of 52 independent spontaneous mutations occurring in a cDNA of the human hypoxanthine phosphoribosyltransferase (hprt) gene, which was integrated into chromosomal DNA of the mouse cell as a part of the retroviral shuttle vector. Spontaneous mutations comprised a variety of events: base substitutions, frameshifts, deletions, duplications, and complex mutational events, and were distributed randomly over the coding region of the gene. Frameshifts were the most frequent mutational event (38%), and base substitutions were the next most frequent (25%), followed by deletions (19%). Frameshift and deletion mutations commonly occurred preferentially at sites flanked by short direct repeats. Short inverted repeats were frequently found to be associated with duplication and complex mutational events. Analysis of the sequence alterations in the mutant genes suggests that misalignment mutagenesis represents an important molecular mechanism for the generation of spontaneous mutations in eukaryotic cells.

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References

Lee G, Savage E, Ritzel R, VON Borstel R . The base-alteration spectrum of spontaneous and ultraviolet radiation-induced forward mutations in the URA3 locus of Saccharomyces cerevisiae. Mol Gen Genet. 1988; 214(3):396-404. DOI: 10.1007/BF00330472. View

Miller J . Mutagenic specificity of ultraviolet light. J Mol Biol. 1985; 182(1):45-65. DOI: 10.1016/0022-2836(85)90026-9. View

Calos M, Lebkowski J, Botchan M . High mutation frequency in DNA transfected into mammalian cells. Proc Natl Acad Sci U S A. 1983; 80(10):3015-9. PMC: 393964. DOI: 10.1073/pnas.80.10.3015. View

Pribnow D, Sigurdson D, Gold L, Singer B, Napoli C, Brosius J . rII cistrons of bacteriophage T4. DNA sequence around the intercistronic divide and positions of genetic landmarks. J Mol Biol. 1981; 149(3):337-76. DOI: 10.1016/0022-2836(81)90477-0. View

Wood R . Pyrimidine dimers are not the principal pre-mutagenic lesions induced in lambda phage DNA by ultraviolet light. J Mol Biol. 1985; 184(4):577-85. DOI: 10.1016/0022-2836(85)90304-3. View

Hanahan D . Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983; 166(4):557-80. DOI: 10.1016/s0022-2836(83)80284-8. View

Farabaugh P, Schmeissner U, Hofer M, Miller J . Genetic studies of the lac repressor. VII. On the molecular nature of spontaneous hotspots in the lacI gene of Escherichia coli. J Mol Biol. 1978; 126(4):847-57. DOI: 10.1016/0022-2836(78)90023-2. View

Drinkwater N, Klinedinst D . Chemically induced mutagenesis in a shuttle vector with a low-background mutant frequency. Proc Natl Acad Sci U S A. 1986; 83(10):3402-6. PMC: 323522. DOI: 10.1073/pnas.83.10.3402. View

Hirt B . Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967; 26(2):365-9. DOI: 10.1016/0022-2836(67)90307-5. View

10.

Ripley L . Model for the participation of quasi-palindromic DNA sequences in frameshift mutation. Proc Natl Acad Sci U S A. 1982; 79(13):4128-32. PMC: 346590. DOI: 10.1073/pnas.79.13.4128. View

11.

Yang T, Patel P, Chinault A, Stout J, Jackson L, Hildebrand B . Molecular evidence for new mutation at the hprt locus in Lesch-Nyhan patients. Nature. 1984; 310(5976):412-4. DOI: 10.1038/310412a0. View

12.

Patel P, Framson P, Caskey C, Chinault A . Fine structure of the human hypoxanthine phosphoribosyltransferase gene. Mol Cell Biol. 1986; 6(2):393-403. PMC: 367528. DOI: 10.1128/mcb.6.2.393-403.1986. View

13.

Stout J, Caskey C . HPRT: gene structure, expression, and mutation. Annu Rev Genet. 1985; 19:127-48. DOI: 10.1146/annurev.ge.19.120185.001015. View

14.

Kunkel T, Soni A . Mutagenesis by transient misalignment. J Biol Chem. 1988; 263(29):14784-9. View

15.

Dush M, Sikela J, Khan S, Tischfield J, Stambrook P . Nucleotide sequence and organization of the mouse adenine phosphoribosyltransferase gene: presence of a coding region common to animal and bacterial phosphoribosyltransferases that has a variable intron/exon arrangement. Proc Natl Acad Sci U S A. 1985; 82(9):2731-5. PMC: 397639. DOI: 10.1073/pnas.82.9.2731. View

16.

Miller A, Jolly D, Friedmann T, Verma I . A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT. Proc Natl Acad Sci U S A. 1983; 80(15):4709-13. PMC: 384113. DOI: 10.1073/pnas.80.15.4709. View

17.

Jolly D, Okayama H, Berg P, Esty A, Filpula D, Bohlen P . Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase. Proc Natl Acad Sci U S A. 1983; 80(2):477-81. PMC: 393401. DOI: 10.1073/pnas.80.2.477. View

18.

Okada Y, Streisinger G, Owen J, Newton J, Tsugita A, Inouye M . Molecular basis of a mutational hot spot in the lysozyme gene of bacteriophage T4. Nature. 1972; 236(5346):338-41. DOI: 10.1038/236338a0. View

19.

Ripley L, Clark A, deBoer J . Spectrum of spontaneous frameshift mutations. Sequences of bacteriophage T4 rII gene frameshifts. J Mol Biol. 1986; 191(4):601-13. DOI: 10.1016/0022-2836(86)90448-1. View

20.

DE Boer J, Ripley L . Demonstration of the production of frameshift and base-substitution mutations by quasipalindromic DNA sequences. Proc Natl Acad Sci U S A. 1984; 81(17):5528-31. PMC: 391739. DOI: 10.1073/pnas.81.17.5528. View