Transpositions and translocations induced by site-specific double-strand breaks in budding yeast

Haber, James E.

doi:10.1016/j.dnarep.2006.05.025

Cited by 60 publications

(47 citation statements)

References 118 publications

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“…An example of Southern blot analysis of MATa switching to MATa is shown in Figure 5. Physical monitoring of recombination at MAT has yielded much of what we know about DSB-induced mitotic recombination (reviewed in Haber 1995Haber , 2006Pâques and Haber 1999;Krogh and Symington 2004;Hicks et al 2011). Some related studies have been done by inserting small HO endonuclease recognition sites at other locations and from the induction of other site-specific endonucleases, most notably I-SceI (Rudin and Haber 1988;Nickoloff et al 1989;Ray et al 1989;Plessis et al 1992;McGill et al 1993;Liefshitz et al 1995;Weng et al 1996;Inbar and Kupiec 1999;Wilson 2002;Storici et al 2003;Lydeard et al 2007Lydeard et al , 2010Jain et al 2009;Marrero and Symington 2010).…”

Section: Mat Switching: a Model For Homologous Recombinationmentioning

confidence: 99%

“…Double-strand breaks (DSBs) in chromosomes can be repaired either by homologous recombination (HR) or by nonhomologous end-joining (NHEJ) (reviewed by Pâques and Haber 1999;Haber 2006). In haploids, both processes are efficient; for example a DSB at MAT created by the HO endonuclease is repaired 90% of the time by HR, using HML or HMR as the donor, but 10% of cells use NHEJ to religate the DSB ends, recreating the cleavage site.…”

Section: Haploid-specific and Diploid-specific Genes Under Mat Controlmentioning

confidence: 99%

“…The two mating-type alleles, MATa and MATa, differ by 700 bp of sequences designated Ya and Ya, respectively ( Figure 2). Ya and Ya contain the promoters and most of the open reading frames for proteins that regulate many aspects of the cell's sexual activity (for reviews, see Klar 1987;Herskowitz 1988;Strathern 1988;Haber 1992Haber , 1998Haber , 2006Haber , 2007. The MAT locus is divided into five regions (W, X, Y, Z1, and Z2) on the basis of sequences that are shared between MAT and the two cryptic copies of mating-type sequences located at HMLa and HMRa (Figure 1).…”

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Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

2012

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Mating type in Saccharomyces cerevisiae is determined by two nonhomologous alleles, MATa and MATa. These sequences encode regulators of the two different haploid mating types and of the diploids formed by their conjugation. Analysis of the MATa1, MATa1, and MATa2 alleles provided one of the earliest models of cell-type specification by transcriptional activators and repressors. Remarkably, homothallic yeast cells can switch their mating type as often as every generation by a highly choreographed, site-specific homologous recombination event that replaces one MAT allele with different DNA sequences encoding the opposite MAT allele. This replacement process involves the participation of two intact but unexpressed copies of mating-type information at the heterochromatic loci, HMLa and HMRa, which are located at opposite ends of the same chromosome-encoding MAT. The study of MAT switching has yielded important insights into the control of cell lineage, the silencing of gene expression, the formation of heterochromatin, and the regulation of accessibility of the donor sequences. Real-time analysis of MAT switching has provided the most detailed description of the molecular events that occur during the homologous recombinational repair of a programmed double-strand chromosome break. TABLE OF CONTENTS Abstract 33Introduction 34

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Section: Mat Switching: a Model For Homologous Recombinationmentioning

confidence: 99%

Section: Haploid-specific and Diploid-specific Genes Under Mat Controlmentioning

confidence: 99%

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Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

2012

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“…However, it has also been recognized that HR also has the potential to induce genome instability, acting inappropriately or in an unregulated fashion (Elliott and Jasin 2002;Kolodner et al 2002). For example, ectopic recombination between repeated DNA is a potent driver of chromosomal rearrangements, as suspected from genomic analysis and established in genetic model systems (Szankasi et al 1986;Cooper et al 1997;Agarwal et al 2006;Haber 2006;Weinstock et al 2006;Putnam et al 2009;Song et al 2014). Furthermore, the identification of synthetic lethality in double mutants that depend on HR, called recombination-dependent lethality, shows that uncontrolled HR leads to potentially toxic intermediates and cell death (Heude et al 1995;Schild 1995;Gangloff et al 2000;Fabre et al 2002;Bastin-Shanower et al 2003).…”

Section: Quality Control By Pathway Reversibilitymentioning

confidence: 99%

Regulation of Recombination and Genomic Maintenance

Heyer

2015

Cold Spring Harb Perspect Biol

104

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Recombination is a central process to stably maintain and transmit a genome through somatic cell divisions and to new generations. Hence, recombination needs to be coordinated with other events occurring on the DNA template, such as DNA replication, transcription, and the specialized chromosomal functions at centromeres and telomeres. Moreover, regulation with respect to the cell-cycle stage is required as much as spatiotemporal coordination within the nuclear volume. These regulatory mechanisms impinge on the DNA substrate through modifications of the chromatin and directly on recombination proteins through a myriad of posttranslational modifications (PTMs) and additional mechanisms. Although recombination is primarily appreciated to maintain genomic stability, the process also contributes to gross chromosomal arrangements and copy-number changes. Hence, the recombination process itself requires quality control to ensure high fidelity and avoid genomic instability. Evidently, recombination and its regulatory processes have significant impact on human disease, specifically cancer and, possibly, neurodegenerative diseases.

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“…2A). Yα and Ya contain the promoters and most of the open reading frames for proteins that regulate many aspects of the cell's sexual activity (for reviews, see 1,2,3,4,5,6). The MAT locus is divided into five regions (W, X, Y, Z1, and Z2) on the basis of sequences that are shared between MAT and the two cryptic copies of mating-type sequences located at HMLα and HMRa (Fig.…”

Section: Introductionmentioning

confidence: 99%

Mating-type Gene Switching in Saccharomyces cerevisiae

Lee

Haber

2015

Microbiol Spectr

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The budding yeast Saccharomyces cerevisiae has two alternative mating types designated MATa and MATα. These are distinguished by about 700 bp of unique sequences, Ya or Yα, including divergent promoter sequences and part of the open reading frames of genes that regulate mating phenotype. Homothallic budding yeast, carrying an active HO endonuclease gene, HO, can switch mating type through a recombination process known as gene conversion, in which a site-specific double-strand break (DSB) created immediately adjacent to the Y region results in replacement of the Y sequences with a copy of the opposite mating type information, which is harbored in one of two heterochromatic donor loci, HMLα or HMRa. HO gene expression is tightly regulated to ensure that only half of the cells in a lineage switch to the opposite MAT allele, thus promoting conjugation and diploid formation. Study of the silencing of these loci has provided a great deal of information about the role of the Sir2 histone deacetylase and its associated Sir3 and Sir4 proteins in creating heterochromatic regions. MAT switching has been examined in great detail to learn about the steps in homologous recombination. MAT switching is remarkably directional, with MATa recombining preferentially with HMLα and MATα using HMRa. Donor preference is controlled by a cis-acting recombination enhancer located near HML. RE is turned off in MATα cells but in MATa binds multiple copies of the Fkh1 transcription factor whose forkhead-associated phosphothreonine binding domain localizes at the DSB, bringing HML into conjunction with MATa.

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Transpositions and translocations induced by site-specific double-strand breaks in budding yeast

Cited by 60 publications

References 118 publications

Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

Regulation of Recombination and Genomic Maintenance

Mating-type Gene Switching in Saccharomyces cerevisiae

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