A Unique Pathway of Double-strand Break Repair Operates in Tandemly Repeated Genes

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1991 Mar 1

PMID 1996088

Citations 106

Authors

B A Ozenberger

G S Roeder

Affiliations

Soon will be listed here.

Abstract

The RAD52 gene product of the yeast Saccharomyces cerevisiae is required for most spontaneous recombination and almost all double-strand break (DSB) repair. In contrast to recombination elsewhere in the genome, recombination in the ribosomal DNA (rDNA) array is RAD52 independent. To determine the fate of a DSB in the rDNA gene array, a cut site for the HO endonuclease was inserted into the rDNA in a strain containing an inducible HO gene. DSBs were efficiently repaired at this site, even in the absence of the RAD52 gene product. Efficient RAD52-independent DSB repair was also observed at another tandem gene array, CUP1, consisting of 18 repeat units. However, in a smaller CUP1 array, consisting of only three units, most DSBs (ca. 80%) were not repaired and resulted in cell death. All RAD52-independent DSB repair events examined resulted in the loss of one or more repeat units. We propose a model for DSB repair in repeated sequences involving the generation of single-stranded tails followed by reannealing.

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References

Weiffenbach B, Rogers D, Haber J, Zoller M, Russell D, Smith M . Deletions and single base pair changes in the yeast mating type locus that prevent homothallic mating type conversions. Proc Natl Acad Sci U S A. 1983; 80(11):3401-5. PMC: 394051. DOI: 10.1073/pnas.80.11.3401. View

Jackson J, Fink G . Gene conversion between duplicated genetic elements in yeast. Nature. 1981; 292(5821):306-11. DOI: 10.1038/292306a0. View

Klein H . Different types of recombination events are controlled by the RAD1 and RAD52 genes of Saccharomyces cerevisiae. Genetics. 1988; 120(2):367-77. PMC: 1203516. DOI: 10.1093/genetics/120.2.367. View

Weiffenbach B, Haber J . Homothallic mating type switching generates lethal chromosome breaks in rad52 strains of Saccharomyces cerevisiae. Mol Cell Biol. 1981; 1(6):522-34. PMC: 369695. DOI: 10.1128/mcb.1.6.522-534.1981. View

Resnick M . The repair of double-strand breaks in DNA; a model involving recombination. J Theor Biol. 1976; 59(1):97-106. DOI: 10.1016/s0022-5193(76)80025-2. View

Bell G, DeGennaro L, Gelfand D, Bishop R, Valenzuela P, Rutter W . Ribosomal RNA genes of Saccharomyces cerevisiae. I. Physical map of the repeating unit and location of the regions coding for 5 S, 5.8 S, 18 S, and 25 S ribosomal RNAs. J Biol Chem. 1977; 252(22):8118-25. View

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

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

Haber J, Hearn M . Rad52-independent mitotic gene conversion in Saccharomyces cerevisiae frequently results in chromosomal loss. Genetics. 1985; 111(1):7-22. PMC: 1202600. DOI: 10.1093/genetics/111.1.7. View

10.

Fogel S, Welch J . Tandem gene amplification mediates copper resistance in yeast. Proc Natl Acad Sci U S A. 1982; 79(17):5342-6. PMC: 346892. DOI: 10.1073/pnas.79.17.5342. View

11.

Byers B, Goetsch L . Electron microscopic observations on the meiotic karyotype of diploid and tetraploid Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1975; 72(12):5056-60. PMC: 388874. DOI: 10.1073/pnas.72.12.5056. 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.

Rudin N, Haber J . Efficient repair of HO-induced chromosomal breaks in Saccharomyces cerevisiae by recombination between flanking homologous sequences. Mol Cell Biol. 1988; 8(9):3918-28. PMC: 365451. DOI: 10.1128/mcb.8.9.3918-3928.1988. View

14.

Alani E, Padmore R, Kleckner N . Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination. Cell. 1990; 61(3):419-36. DOI: 10.1016/0092-8674(90)90524-i. View

15.

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

16.

Resnick M . The repair of double-strand breaks in chromosomal DNA of yeast. Basic Life Sci. 1975; 5B:549-56. DOI: 10.1007/978-1-4684-2898-8_20. View

17.

Resnick M . Genetic control of radiation sensitivity in Saccharomyces cerevisiae. Genetics. 1969; 62(3):519-31. PMC: 1212294. DOI: 10.1093/genetics/62.3.519. View

18.

Nicolas A, Szostak J . Gene conversion adjacent to regions of double-strand break repair. Mol Cell Biol. 1988; 8(12):5292-8. PMC: 365631. DOI: 10.1128/mcb.8.12.5292-5298.1988. View

19.

Jensen R, Sprague Jr G, Herskowitz I . Regulation of yeast mating-type interconversion: feedback control of HO gene expression by the mating-type locus. Proc Natl Acad Sci U S A. 1983; 80(10):3035-9. PMC: 393968. DOI: 10.1073/pnas.80.10.3035. View

20.

Rockmill B, Roeder G . RED1: a yeast gene required for the segregation of chromosomes during the reductional division of meiosis. Proc Natl Acad Sci U S A. 1988; 85(16):6057-61. PMC: 281904. DOI: 10.1073/pnas.85.16.6057. View