Mating-Type Genes and<i>MAT</i>Switching in<i>Saccharomyces cerevisiae</i>

Haber, James E.

doi:10.1534/genetics.111.134577

Cited by 378 publications

(362 citation statements)

References 340 publications

(358 reference statements)

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“…The fusion of two haploid cells of opposite mating types generates a diploid cell that subsequently undergoes meiosis, generating haploid cells with new genetic assortments. 38 Here, we report that yeast pheromones can stimulate the relocalization of the CRT ortholog Cne1p to the cell periphery, and that Cne1p is required for optimal mating, in particular in shaking cultures (in which stable intercellular contacts are rather difficult to be achieved). Our results indicate that Cne1p is not absolutely required for mating but facilitates cell-to-cell conjugation, in line with previous observations on the role of surface-exposed CRT in the fertilization of oocytes by sperm cells.…”

Section: Discussionmentioning

confidence: 95%

Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8

Sukkurwala¹,

Martins²,

Wang³

et al. 2013

Cell Death Differ

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The exposure of calreticulin (CRT) on the surface of stressed and dying cancer cells facilitates their uptake by dendritic cells and the subsequent presentation of tumor-associated antigens to T lymphocytes, hence stimulating an anticancer immune response. The chemotherapeutic agent mitoxantrone (MTX) can stimulate the peripheral relocation of CRT in both human and yeast cells, suggesting that the CRT exposure pathway is phylogenetically conserved. Here, we show that pheromones can act as physiological inducers of CRT exposure in yeast cells, thereby facilitating the formation of mating conjugates, and that a largespectrum inhibitor of G protein-coupled receptors (which resemble the yeast pheromone receptor) prevents CRT exposure in human cancer cells exposed to MTX. An RNA interference screen as well as transcriptome analyses revealed that chemokines, in particular human CXCL8 (best known as interleukin-8) and its mouse ortholog Cxcl2, are involved in the immunogenic translocation of CRT to the outer leaflet of the plasma membrane. MTX stimulated the production of CXCL8 by human cancer cells in vitro and that of Cxcl2 by murine tumors in vivo. The knockdown of CXCL8/Cxcl2 receptors (CXCR1/Cxcr1 and Cxcr2) reduced MTX-induced CRT exposure in both human and murine cancer cells, as well as the capacity of the latter-on exposure to MTX-to elicit an anticancer immune response in vivo. Conversely, the addition of exogenous Cxcl2 increased the immunogenicity of dying cells in a CRT-dependent manner. Altogether, these results identify autocrine and paracrine chemokine signaling circuitries that modulate CRT exposure and the immunogenicity of cell death.

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Section: Discussionmentioning

confidence: 95%

Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8

Sukkurwala¹,

Martins²,

Wang³

et al. 2013

Cell Death Differ

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“…S2) and placed the peak signal from chromosome 3 at position 897 kb, which is 3 kb from the leftmost IR and 5 kb from the MATalpha genes. The centromeric region is transcriptionally silent (SI Appendix, (3,4,(12)(13)(14)(15)(16)(17)(18). Saccharomycotina, Pezizomycotina, and Taphrinomycotina are subphyla within phylum Ascomycota (19).…”

Section: Resultsmentioning

confidence: 99%

“…Hansenula polymorpha | Pichia pastoris | yeast genetics | comparative genomics M ating-type switching in yeasts is a highly regulated process that converts a haploid cell of one mating type into a haploid of the opposite type (1)(2)(3)(4)(5). Switching involves the complete deactivation of one set of regulatory genes and activation of an alternative set, but, unlike most regulatory changes, the switch is achieved by physically replacing the DNA at an expression site that is shared by both types of cell.…”

mentioning

confidence: 99%

“…Despite their apparently independent origins, the switching systems of S. cerevisiae (3) and S. pombe (4, 5) have many parallels, including the presence of three MAT-like loci (two of which are silenced) with triplicated guide sequences, a mechanism for specifically inducing a DNA break at MAT, donor bias (27), and cell-lineage tracking. However, the details of switching and silencing are quite different in the two species (3,4).…”

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confidence: 99%

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Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locusSaccharomyces cerevisiaesystem

Hanson

Byrne

Wolfe

2014

Proc. Natl. Acad. Sci. U.S.A.

150

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Saccharomyces cerevisiae has a complex system for switching the mating type of haploid cells, requiring the genome to have three mating-type (MAT)-like loci and a mechanism for silencing two of them. How this system originated is unknown, because the threelocus system is present throughout the family Saccharomycetaceae, whereas species in the sister Candida clade have only one locus and do not switch. Here we show that yeasts in a third clade, the methylotrophs, have a simpler two-locus switching system based on reversible inversion of a section of chromosome with MATa genes at one end and MATalpha genes at the other end. In Hansenula polymorpha the 19-kb invertible region lies beside a centromere so that, depending on the orientation, either MATa or MATalpha is silenced by centromeric chromatin. In Pichia pastoris, the orientation of a 138-kb invertible region puts either MATa or MATalpha beside a telomere and represses transcription of MATa2 or MATalpha2. Both species are homothallic, and inversion of their MAT regions can be induced by crossing two strains of the same mating type. The three-locus system of S. cerevisiae, which uses a nonconservative mechanism to replace DNA at MAT, likely evolved from a conservative two-locus system that swapped genes between expression and nonexpression sites by inversion. The increasing complexity of the switching apparatus, with three loci, donor bias, and cell lineage tracking, can be explained by continuous selection to increase sporulation ability in young colonies. Our results provide an evolutionary context for the diversity of switching and silencing mechanisms.Hansenula polymorpha | Pichia pastoris | yeast genetics | comparative genomics M ating-type switching in yeasts is a highly regulated process that converts a haploid cell of one mating type into a haploid of the opposite type (1-5). Switching involves the complete deactivation of one set of regulatory genes and activation of an alternative set, but, unlike most regulatory changes, the switch is achieved by physically replacing the DNA at an expression site that is shared by both types of cell. In Saccharomyces cerevisiae the switching system uses a menagerie of molecular components (3) including three mating-type (MAT)-like loci (the expressed MAT locus and the silent loci HML and HMR); an endonuclease (HO) that creates a double-strand break at the MAT locus, which then is repaired using HMLalpha or HMRa as a donor; a mechanism (Sir1 and Sir2/3/4 proteins) for repressing transcription and HO cleavage at the silent loci; two triplicated sequences (the Z and X regions) that guide repair of the dsDNA break; a donorbias mechanism (the recombination enhancer, RE) to ensure that switching happens in the correct direction; and a cell lineagetracking mechanism (Ash1 mRNA localization) to ensure that switching occurs only in particular cells. Most of these components have no function other than facilitating switching.

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“…Fkh1 has also been implicated as a regulator of mating-type switching, which involves homologous recombination between distal chromosomal loci (reviewed in ref. 8). Fkh1 and Fkh2 have been most extensively characterized as transcription factors that control groups of cell cycle control genes, particularly the "cyclin B 2 (CLB2) cluster" genes (reviewed in ref.…”

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confidence: 99%

Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

Ostrow

Kalhor

Gan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Forkhead Box (Fox) proteins share the Forkhead domain, a wingedhelix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified Saccharomyces cerevisiae Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2) as required for the clustering of a subset of replication origins in G 1 phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity. Here, we show that Fkh1 and Fkh2 share a unique structural feature of human FoxP proteins that enables FoxP2 and FoxP3 to form domain-swapped dimers capable of bridging two DNA molecules in vitro. Accordingly, Fkh1 self-associates in vitro and in vivo in a manner dependent on the conserved domain-swapping region, strongly suggestive of homodimer formation. Fkh1-and Fkh2-domain-swap-minus (dsm) mutations are functional as transcription factors yet are defective in replication origin timing control. Fkh1-dsm binds replication origins in vivo but fails to cluster them, supporting the conclusion that Fkh1 and Fkh2 dimers perform a structural role in the spatial organization of chromosomal elements with functional importance.DNA replication timing | chromatin | nuclear organization | Fox proteins | DNA binding protein F undamental processes of DNA repair, recombination, transcription, and replication often occur in specific subnuclear domains or in localized foci (reviewed in refs. 1-4). In yeast for example, hundreds of highly expressed tRNA genes coalesce into multiple foci, each containing several active tRNA genes (reviewed in ref. 5). Similarly, hundreds of replication origins coalesce into foci containing several origins each, which become bidirectional replisomes that remain colocalized as DNA is spooled through during replication (reviewed in ref. 6). Such spatial organization is thought to contribute to the efficiency of these processes by increasing the local concentration of the involved factors, which may consequently also exclude competing or interfering factors or processes. How distal DNA sequences are assembled into these structures is poorly understood.We recently identified the Saccharomyces cerevisiae transcription factors Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2) as being required for the clustering of a subset of replication origins in G 1 phase and for the early initiation of these origins in the ensuing S phase (7). How Fkh1 and Fkh2 promote clustering is unclear; however, their binding near origins might promote origin-origin interactions through binding to other proteins at origins, such as the origin recognition complex (ORC) (7). Fkh1 has also been implicated as a regulator of mating-type switching, which involves homologous recombination between distal chr...

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Mating-Type Genes andMATSwitching inSaccharomyces cerevisiae

Cited by 378 publications

References 340 publications

Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8

Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8

Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locusSaccharomyces cerevisiaesystem

Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

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