Transcription Enhances Intrachromosomal Homologous Recombination in Mammalian Cells

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1992 Dec 1

PMID 1333040

Citations 56

Authors

J A Nickoloff

Affiliations

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Abstract

The influence of transcription on homologous intrachromosomal recombination between direct and inverted repeats has been examined by using Chinese hamster ovary cells. Recombination was monitored between two integrated neomycin (neo) genes, including one silent allele and a second allele regulated by the inducible mouse mammary tumor virus promoter. Transcription of mouse mammary tumor virus neo alleles was regulated with the glucocorticoid hormone dexamethasone. Alleles transcribed at high levels recombined about two- to sevenfold more frequently than identical alleles transcribed at low levels. Direct repeats recombined primarily by a gene conversion mechanism; inverted repeats produced a variety of rearranged products. These results are discussed in relation to recombinational processes that regulate gene expression, influence gene family structures, and mediate genomic instability associated with cellular transformation and tumorigenesis.

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References

Lin F, Sperle K, Sternberg N . Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process. Mol Cell Biol. 1984; 4(6):1020-34. PMC: 368869. DOI: 10.1128/mcb.4.6.1020-1034.1984. View

Klar A, Strathern J, Hicks J . A position-effect control for gene transposition: state of expression of yeast mating-type genes affects their ability to switch. Cell. 1981; 25(2):517-24. DOI: 10.1016/0092-8674(81)90070-2. View

Ringold G, Yamamoto K, Bishop J, Varmus H . Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA. Proc Natl Acad Sci U S A. 1977; 74(7):2879-83. PMC: 431330. DOI: 10.1073/pnas.74.7.2879. View

Shenkar R, Shen M, Arnheim N . DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot. Mol Cell Biol. 1991; 11(4):1813-9. PMC: 359851. DOI: 10.1128/mcb.11.4.1813-1819.1991. View

Grimm C, Schaer P, Munz P, Kohli J . The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe. Mol Cell Biol. 1991; 11(1):289-98. PMC: 359619. DOI: 10.1128/mcb.11.1.289-298.1991. View

Roeder G . Gene conversion tracts stimulated by HOT1-promoted transcription are long and continuous. Genetics. 1990; 126(4):851-67. PMC: 1204283. DOI: 10.1093/genetics/126.4.851. View

Roeder G . A chromosome containing HOT1 preferentially receives information during mitotic interchromosomal gene conversion. Genetics. 1990; 124(3):561-72. PMC: 1203949. DOI: 10.1093/genetics/124.3.561. View

Johnson R, Sheng M, Greenberg M, Kolodner R, Papaioannou V, Spiegelman B . Targeting of nonexpressed genes in embryonic stem cells via homologous recombination. Science. 1989; 245(4923):1234-6. DOI: 10.1126/science.2506639. View

Wallis J, Chrebet G, Brodsky G, Rolfe M, Rothstein R . A hyper-recombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase. Cell. 1989; 58(2):409-19. DOI: 10.1016/0092-8674(89)90855-6. View

10.

Nickoloff J, Singer J, Hoekstra M, Heffron F . Double-strand breaks stimulate alternative mechanisms of recombination repair. J Mol Biol. 1989; 207(3):527-41. DOI: 10.1016/0022-2836(89)90462-2. View

11.

Thomas B, Rothstein R . The genetic control of direct-repeat recombination in Saccharomyces: the effect of rad52 and rad1 on mitotic recombination at GAL10, a transcriptionally regulated gene. Genetics. 1989; 123(4):725-38. PMC: 1203884. DOI: 10.1093/genetics/123.4.725. View

12.

Christman M, Dietrich F, Fink G . Mitotic recombination in the rDNA of S. cerevisiae is suppressed by the combined action of DNA topoisomerases I and II. Cell. 1988; 55(3):413-25. DOI: 10.1016/0092-8674(88)90027-x. View

13.

Emerman M, Temin H . Quantitative analysis of gene suppression in integrated retrovirus vectors. Mol Cell Biol. 1986; 6(3):792-800. PMC: 367579. DOI: 10.1128/mcb.6.3.792-800.1986. View

14.

Alt F, Blackwell T, DePinho R, Reth M, Yancopoulos G . Regulation of genome rearrangement events during lymphocyte differentiation. Immunol Rev. 1986; 89:5-30. DOI: 10.1111/j.1600-065x.1986.tb01470.x. View

15.

Mansour S, Thomas K, Capecchi M . Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988; 336(6197):348-52. DOI: 10.1038/336348a0. View

16.

Keil R, Roeder G . Recombination-stimulating sequences in yeast ribosomal DNA correspond to sequences regulating transcription by RNA polymerase I. Cell. 1987; 48(6):1071-9. DOI: 10.1016/0092-8674(87)90714-8. View

17.

Emerman M, Temin H . Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell. 1984; 39(3 Pt 2):449-67. View

18.

Southern P, Berg P . Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982; 1(4):327-41. View

19.

Ikeda H, Matsumoto T . Transcription promotes recA-independent recombination mediated by DNA-dependent RNA polymerase in Escherichia coli. Proc Natl Acad Sci U S A. 1979; 76(9):4571-5. PMC: 411620. DOI: 10.1073/pnas.76.9.4571. View

20.

Deng W, Nickoloff J . Site-directed mutagenesis of virtually any plasmid by eliminating a unique site. Anal Biochem. 1992; 200(1):81-8. DOI: 10.1016/0003-2697(92)90280-k. View