Recombination Between DNA Repeats in Yeast Hpr1delta Cells is Linked to Transcription Elongation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1997 May 15

PMID 9184227

Citations 55

Authors

F Prado

J I Piruat

A Aguilera

Affiliations

Soon will be listed here.

Abstract

The induction of recombination by transcription activation has been documented in prokaryotes and eukaryotes. Unwinding of the DNA duplex, disruption of chromatin structure or changes in local supercoiling associated with transcription can be indirectly responsible for the stimulation of recombination. Here we provide genetic and molecular evidence for a specific mechanism of stimulation of recombination by transcription. We show that the induction of deletions between repeats in hpr1delta cells of Saccharomyces cerevisiae is linked to transcription elongation. Molecular analysis of different direct repeat constructs reveals that deletions induced by hpr1delta are specific for repeat constructs in which transcription initiating at an external promoter traverses particular regions of the DNA flanked by the repeats. Transcription becomes HPR1 dependent when elongating through such regions. Both the induction of deletions and the HPR1 dependence of transcription were abolished when a strong terminator was used to prevent transcription from proceeding through the DNA region flanked by the repeats. In contrast to previously reported cases of transcription-induced recombination, there was no correlation between high levels of transcripts and high levels of recombination. Our study provides evidence that direct repeat recombination can be induced by transcriptional elongation.

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References

Vilette D, Uzest M, Ehrlich S, Michel B . DNA transcription and repressor binding affect deletion formation in Escherichia coli plasmids. EMBO J. 1992; 11(10):3629-34. PMC: 556822. DOI: 10.1002/j.1460-2075.1992.tb05447.x. View

Forrester K, Almoguera C, Han K, Grizzle W, Perucho M . Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature. 1987; 327(6120):298-303. DOI: 10.1038/327298a0. View

Fan H, Cheng K, Klein H . Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae. Genetics. 1996; 142(3):749-59. PMC: 1207016. DOI: 10.1093/genetics/142.3.749. View

Struhl K, Stinchcomb D, Scherer S, Davis R . High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules. Proc Natl Acad Sci U S A. 1979; 76(3):1035-9. PMC: 383183. DOI: 10.1073/pnas.76.3.1035. 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

Prado F, Aguilera A . Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes. Genetics. 1995; 139(1):109-23. PMC: 1206311. DOI: 10.1093/genetics/139.1.109. View

Thomas P . Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980; 77(9):5201-5. PMC: 350025. DOI: 10.1073/pnas.77.9.5201. View

Ross J . Control of messenger RNA stability in higher eukaryotes. Trends Genet. 1996; 12(5):171-5. DOI: 10.1016/0168-9525(96)10016-0. View

BOURGAUX-RAMOISY D, Gendron D, BOURGAUX P . A hotspot for promoter-dependent recombination in polyomavirus DNA. J Mol Biol. 1995; 248(2):220-4. DOI: 10.1016/s0022-2836(95)80044-1. View

10.

Sikorski R, Hieter P . A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989; 122(1):19-27. PMC: 1203683. DOI: 10.1093/genetics/122.1.19. View

11.

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

12.

White M, Dominska M, Petes T . Transcription factors are required for the meiotic recombination hotspot at the HIS4 locus in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993; 90(14):6621-5. PMC: 46984. DOI: 10.1073/pnas.90.14.6621. View

13.

Zhu Y, Peterson C, Christman M . HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1995; 15(3):1698-708. PMC: 230394. DOI: 10.1128/MCB.15.3.1698. View

14.

Gottlieb S, Esposito R . A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell. 1989; 56(5):771-6. DOI: 10.1016/0092-8674(89)90681-8. View

15.

Uemura H, Pandit S, Jigami Y, Sternglanz R . Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Genetics. 1996; 142(4):1095-103. PMC: 1207110. DOI: 10.1093/genetics/142.4.1095. View

16.

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

17.

Nicolas A, Treco D, Schultes N, Szostak J . An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae. Nature. 1989; 338(6210):35-9. DOI: 10.1038/338035a0. View

18.

Thomas B, Rothstein R . Elevated recombination rates in transcriptionally active DNA. Cell. 1989; 56(4):619-30. DOI: 10.1016/0092-8674(89)90584-9. View

19.

Clever B, Heyer W, Aguilera A . The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required for spontaneous and hpr1-induced deletions between direct repeats. Genetics. 1996; 142(3):705-16. PMC: 1207012. DOI: 10.1093/genetics/142.3.705. View

20.

Kupiec M . Transcriptional induction of Ty recombination in yeast. Proc Natl Acad Sci U S A. 1994; 91(26):12711-5. PMC: 45509. DOI: 10.1073/pnas.91.26.12711. View