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Accueil > Départements > Biologie des Génomes > Robert DEBUCHY & Fabienne MALAGNAC : Différenciation sexuée et méiose chez les champignons

Publications thématiques :Rôle de la recombinaison méiotique dans la reconnaissance et l’appariement des chromosomes homologues.


  • S. Tessé, H. - M. Bourbon, R. Debuchy, K. Budin, E. Dubois, Z. Liangran, R. Antoine, T. Piolot, N. Kleckner, D. Zickler, et E. Espagne, « Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination, pairing, and global chromosome compaction », Genes & Development, oct. 2017.
    Résumé : Meiosis is the cellular program by which a diploid cell gives rise to haploid gametes for sexual reproduction. Meiotic progression depends on tight physical and functional coupling of recombination steps at the DNA level with specific organizational features of meiotic-prophase chromosomes. The present study reveals that every step of this coupling is mediated by a single molecule: Asy2/Mer2. We show that Mer2, identified so far only in budding and fission yeasts, is in fact evolutionarily conserved from fungi (Mer2/Rec15/Asy2/Bad42) to plants (PRD3/PAIR1) and mammals (IHO1). In yeasts, Mer2 mediates assembly of recombination-initiation complexes and double-strand breaks (DSBs). This role is conserved in the fungus Sordaria However, functional analysis of 13 mer2 mutants and successive localization of Mer2 to axis, synaptonemal complex (SC), and chromatin revealed, in addition, three further important functions. First, after DSB formation, Mer2 is required for pairing by mediating homolog spatial juxtaposition, with implications for crossover (CO) patterning/interference. Second, Mer2 participates in the transfer/maintenance and release of recombination complexes to/from the SC central region. Third, after completion of recombination, potentially dependent on SUMOylation, Mer2 mediates global chromosome compaction and post-recombination chiasma development. Thus, beyond its role as a recombinosome-axis/SC linker molecule, Mer2 has important functions in relation to basic chromosome structure.
    Mots-clés : chromatin compaction SUMOylation, DBG, DSMC, Meiosis, Mer2, Pairing, Recombination, Sordaria.

  • S. Wang, T. Hassold, P. Hunt, M. A. White, D. Zickler, N. Kleckner, et L. Zhang, « Inefficient Crossover Maturation Underlies Elevated Aneuploidy in Human Female Meiosis », Cell, vol. 168, nᵒ 6, p. 977-989.e17, mars 2017.
    Résumé : Meiosis is the cellular program that underlies gamete formation. For this program, crossovers between homologous chromosomes play an essential mechanical role to ensure regular segregation. We present a detailed study of crossover formation in human male and female meiosis, enabled by modeling analysis. Results suggest that recombination in the two sexes proceeds analogously and efficiently through most stages. However, specifically in female (but not male), ∼25% of the intermediates that should mature into crossover products actually fail to do so. Further, this "female-specific crossover maturation inefficiency" is inferred to make major contributions to the high level of chromosome mis-segregation and resultant aneuploidy that uniquely afflicts human female oocytes (e.g., giving Down syndrome). Additionally, crossover levels on different chromosomes in the same nucleus tend to co-vary, an effect attributable to global per-nucleus modulation of chromatin loop size. Maturation inefficiency could potentially reflect an evolutionary advantage of increased aneuploidy for human females.
    Mots-clés : DBG, DSMC.


  • K. Bomblies, G. Jones, C. Franklin, D. Zickler, et N. Kleckner, « The challenge of evolving stable polyploidy: could an increase in "crossover interference distance" play a central role? », Chromosoma, vol. 125, nᵒ 2, p. 287-300, juin 2016.
    Résumé : Whole genome duplication is a prominent feature of many highly evolved organisms, especially plants. When duplications occur within species, they yield genomes comprising multiple identical or very similar copies of each chromosome ("autopolyploids"). Such genomes face special challenges during meiosis, the specialized cellular program that underlies gamete formation for sexual reproduction. Comparisons between newly formed (neo)-autotetraploids and fully evolved autotetraploids suggest that these challenges are solved by specific restrictions on the positions of crossover recombination events and, thus, the positions of chiasmata, which govern the segregation of homologs at the first meiotic division. We propose that a critical feature in the evolution of these more effective chiasma patterns is an increase in the effective distance of meiotic crossover interference, which plays a central role in crossover positioning. We discuss the findings in several organisms, including the recent identification of relevant genes in Arabidopsis arenosa, that support this hypothesis.
    Mots-clés : Chiasmata, Chromosomes, Plant, Crossing Over, Genetic, Crossover interference, DBG, DSMC, Evolution, Molecular, Homologous chromosomes, Meiosis, plants, Polyploidy, Recombination.

  • H. Takano-Rojas, D. Zickler, et L. Peraza-Reyes, « Peroxisome dynamics during development of the fungus Podospora anserina », Mycologia, vol. 108, nᵒ 3, p. 590-602, juin 2016.
    Résumé : Peroxisomes are versatile and dynamic organelles that are required for the development of diverse eukaryotic organisms. We demonstrated previously that in the fungus Podospora anserina different peroxisomal functions are required at distinct stages of sexual development, including the initiation and progression of meiocyte (ascus) development and the differentiation and germination of sexual spores (ascospores). Peroxisome assembly during these processes relies on the differential activity of the protein machinery that drives the import of proteins into the organelle, indicating a complex developmental regulation of peroxisome formation and activity. Here we demonstrate that peroxisome dynamics is also highly regulated during development. We show that peroxisomes in P. anserina are highly dynamic and respond to metabolic and environmental cues by undergoing changes in size, morphology and number. In addition, peroxisomes of vegetative and sexual cell types are structurally different. During sexual development peroxisome number increases at two stages: at early ascus differentiation and during ascospore formation. These processes are accompanied by changes in peroxisome structure and distribution, which include a cell-polarized concentration of peroxisomes at the beginning of ascus development, as well as a morphological transition from predominantly spherical to elongated shapes at the end of the first meiotic division. Further, the mostly tubular peroxisomes present from second meiotic division to early ascospore formation again become rounded during ascospore differentiation. Ultimately the number of peroxisomes dramatically decreases upon ascospore maturation. Our results reveal a precise regulation of peroxisome dynamics during sexual development and suggest that peroxisome constitution and function during development is defined by the coordinated regulation of the proteins that control peroxisome assembly and dynamics.
    Mots-clés : Cell Differentiation, DBG, DSMC, Fungal Proteins, Fungi, Gene Expression Regulation, Developmental, Gene Expression Regulation, Fungal, Genes, Mating Type, Fungal, Meiosis, peroxisome dynamics, Peroxisomes, Podospora, sexual development, Spores, Fungal.

  • D. Zickler et E. Espagne, « Sordaria, a model system to uncover links between meiotic pairing and recombination », Seminars in Cell & Developmental Biology, vol. 54, p. 149-157, juin 2016.
    Résumé : The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination.
    Mots-clés : Bouquet, DBG, DSMC, Meiotic recombination, Pairing, Sordaria, Synaptonemal Complex.

  • D. Zickler et N. Kleckner, « A few of our favorite things: Pairing, the bouquet, crossover interference and evolution of meiosis », Seminars in Cell & Developmental Biology, vol. 54, p. 135-148, 2016.
    Mots-clés : Bouquet, Crossover interference, DBG, DSMC, Meiosis, Pairing.


  • Z. Liang, D. Zickler, M. Prentiss, F. S. Chang, G. Witz, K. Maeshima, et N. Kleckner, « Chromosomes Progress to Metaphase in Multiple Discrete Steps via Global Compaction/Expansion Cycles », Cell, vol. 161, nᵒ 5, p. 1124-1137, mai 2015.
    Résumé : Mammalian mitotic chromosome morphogenesis was analyzed by 4D live-cell and snapshot deconvolution fluorescence imaging. Prophase chromosomes, whose organization was previously unknown, are revealed to comprise co-oriented sister linear loop arrays displayed along a single, peripheral, regularly kinked topoisomerase II/cohesin/condensin II axis. Thereafter, rather than smooth, progressive compaction as generally envisioned, progression to metaphase is a discontinuous process involving chromosome expansion as well as compaction. At late prophase, dependent on topoisomerase II and with concomitant cohesin release, chromosomes expand, axes split and straighten, and chromatin loops transit to a radial disposition around now-central axes. Finally, chromosomes globally compact, giving the metaphase state. These patterns are consistent with the hypothesis that the molecular events of chromosome morphogenesis are governed by accumulation and release of chromosome stress, created by chromatin compaction and expansion. Chromosome state could evolve analogously throughout the cell cycle.
    Mots-clés : Adenosine Triphosphatases, Animals, Cell Cycle Proteins, Cell Line, Chromosomal Proteins, Non-Histone, Chromosomes, Mammalian, DBG, Deer, DNA Topoisomerases, Type II, DNA-Binding Proteins, DSMC, HeLa Cells, Humans, Metaphase, Microscopy, Fluorescence, Mitosis, Multiprotein Complexes, Swine.

  • S. Wang, D. Zickler, N. Kleckner, et L. Zhang, « Meiotic crossover patterns: Obligatory crossover, interference and homeostasis in a single process », Cell Cycle, vol. 14, nᵒ 3, p. 305-314, 2015.

  • D. Zickler et N. Kleckner, « Recombination, Pairing, and Synapsis of Homologs during Meiosis », Cold Spring Harbor Perspectives in Biology, vol. 7, nᵒ 6, mai 2015.
    Résumé : Recombination is a prominent feature of meiosis in which it plays an important role in increasing genetic diversity during inheritance. Additionally, in most organisms, recombination also plays mechanical roles in chromosomal processes, most notably to mediate pairing of homologous chromosomes during prophase and, ultimately, to ensure regular segregation of homologous chromosomes when they separate at the first meiotic division. Recombinational interactions are also subject to important spatial patterning at both early and late stages. Recombination-mediated processes occur in physical and functional linkage with meiotic axial chromosome structure, with interplay in both directions, before, during, and after formation and dissolution of the synaptonemal complex (SC), a highly conserved meiosis-specific structure that links homolog axes along their lengths. These diverse processes also are integrated with recombination-independent interactions between homologous chromosomes, nonhomology-based chromosome couplings/clusterings, and diverse types of chromosome movement. This review provides an overview of these diverse processes and their interrelationships.
    Mots-clés : Animals, Chromosome Pairing, Chromosomes, DBG, DNA Breaks, Double-Stranded, DSMC, Humans, Meiosis, Recombination, Genetic, Synaptonemal Complex.
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Publications Principales avant 2015

- Zhang L, Espagne E, de Muyt A, Zickler D and Kleckner NE (2014) Interference-mediated synaptonemal complex formation with embedded crossover designation. Proc Natl Acad Sci U S A. 111:E5059-68.

- Vasnier C, de Muyt A, Zhang L, Tessé S, Kleckner NE, Zickler D and Espagne E (2014) Absence of SUN-domain protein Slp1 blocks karyogamy and switches meiotic recombination and synapsis from homologs to sister chromatids. Proc Natl Acad Sci U S A.111:E4015-23.

- De Muyt A, Zhang L, Piolot T, Kleckner N, Espagne E and Zickler D (2014) E3 ligase Hei10 : a multifaceted structure-based signaling molecule with roles within and beyond meiosis. Genes Dev. 28:1111-23.

- Grognet P, Bidard F, Kuchly C, Tong LC, Coppin E, Benkhali JA, Couloux A, Wincker P, Debuchy R and Silar P. (2014) Maintaining two mating types : structure of the mating type locus and its role in heterokaryosis in Podospora anserina. Genetics. 197(1):421-32. doi : 10.1534/genetics.113.159988.

- Cheeseman K, Ropars J, Renault P, Dupont J, Gouzy J, Branca A, Abraham AL, Ceppi M, Conseiller E, Debuchy R, Malagnac F, Goarin A, Silar P, Lacoste S, Sallet E, Bensimon A, Giraud T and Brygoo Y (2014) Multiple recent horizontal transfers of a large genomic region in cheese making fungi. Nat Commun.5:2876.doi : 10.1038/ncomms3876.

- Kleckner N, Zickler D and Witz G (2013) Molecular biology. Chromosome capture brings it all together. Science 342:940-941.

- Ait Benkhali J, Coppin E, Brun S, Peraza-Reyes L, Martin T, Dixelius C, Lazar N, van Tilbeurgh H and Debuchy R (2013) A network of HMG-box transcription factors regulates sexual cycle in the fungus Podospora anserina. PLoS Genet. 9 : e1003642.

- Espagne E, Vasnier C, Storlazzi A, Kleckner N, Silar P, Zickler D and Malagnac F (2011) Sme4 coiled-coil protein mediates synaptonemal complex assembly, recombinosomerelocalization and spindle pole body morphogenesis. Proc Natl Acad Sci U S A. 26 : 10614-10619.

- Kleckner N, Zhang L, Weiner B and Zickler D (2011) Meiotic chromosome dynamics.Chapter 19 in « Genome Organization », pp1-82, ed. Rippe, John Wiley-VCH Verlag, Mannheim.

- Storlazzi A, Gargano S, Ruprich-Robert G, Falque M, David M, Kleckner N and Zickler D. (2010) Recombination proteins mediate meiotic spatial chromosome organization and pairing, Cell 141(1) : 94-106.

- Nowrousian M, Stajich JE, Chu M, Engh I, Espagne E, Halliday K, Kamerewerd J, Kempken F, Knab B, Kuo HC, Osiewacz HD, Pöggeler S, Read ND, Seiler S, Smith KM, Zickler D, Kück U and Freitag M (2010) De novo assembly of a 40 Mb eukaryotic genome from short sequence reads : Sordaria macrospora, a model organism for fungal morphogenesis, PLoS Genet. 6:e1000891.

- Zickler D (2009) Observing meiosis in filamentous fungi :Sordaria and Neurospora, Methods Mol Biol. 558, 91-114, S. Keeney ed. The Human Press Inc. Totowa, New Jersey, USA.

- Storlazzi A, Tesse S, Ruprich-Robert G, Gargano S, Poggeler S, Kleckner N and Zickler D.(2008) Coupling meiotic chromosome axis integrity to recombination, Genes Dev. 22 : 796-809.

- Espagne E, Lespinet O, Malagnac F et al (2008) The genome sequence of the model ascomycete fungus Podospora anserina.Genome Biol. 9:R77.

- Zickler D (2006) From early homologue recognition to synaptonemal complex formation, Chromosoma 115:158-174.

- Shiu PK, Zickler D, Raju NB, Ruprich-Robert G and Metzenberg RL (2006) SAD-2 is required for meiotic silencing by unpaired DNA and perinuclear localization of SAD-1 RNA-directed RNA polymerase, Proc Natl Acad Sci U S A. 103 : 2243-2248.

- Zickler D (2006) Meiosis in mycelialfungi. pp 415-438. The Mycota I. Growth, differentiation and sexuality. U. Kües and R. Fischer eds. Springer -Verlag Berlin Heidelberg.

- Kleckner, Zickler D, Jones GH, Henle J, Dekker J and Hutchinson J (2004) A mechanical basis for chromosome function, Proc Natl Acad Sci U S A.101 : 12592-12597.

- Bishop DK and Zickler D (2004) Meiotic crossover interference prior to stable strand exchange and synapsis, Cell 117:9-15.

- Storlazzi A, Tesse S, Gargano S, James F, Kleckner N and Zickler D (2003) Meiotic double-strand breaks at the interface of chromosome movement, chromosome remodeling, and reductional division. Genes Dev. 17:2675–2687.

- Kleckner N, Storlazzi A and Zickler D (2003) Coordinate variation in meiotic pachytene SC length and total crossover/chiasma frequency under conditions of constant DNA length. Trends Genet. 19(11):623-628.

- Storlazzi A, Tessé S, Gargano S, James F, Kleckner N and Zickler D (2003) Meiotic double-strand breaks at the interface of chromosome movement, chromosome remodeling, and reductional division. Genes Dev. 17, 2675-2687.

- Tessé S, Storlazzi A, Kleckner N, Gargano S and Zickler D (2003) Localization and roles of Ski8p protein in Sordaria meiosis and delineation of three mechanistically distinct steps of meiotic homolog juxtaposition. Proc Natl Acad Sci U S A. 100, 12865-12870.

- van Heemst D, Kafer E, John T, Heyting C, van Aalderen M and Zickler D (2001) BimD/SPO76 is at the interface of cell cycle progression, chromosome morphogenesis, and recombination. Proc Natl Acad Sci U S A. 98, 6267-6272.

- van Heemst D, James F, Pöggeler S, Berteaux-Lecellier V and Zickler D (1999) Spo76p is a conserved chromosome morphogenesis protein that links the mitotic and meiotic programs. Cell 98, 261-271.

- Zickler D and Kleckner N (1999) Meiotic chromosomes : integrating structure and function. Annu. Rev. Genet. 33, 603-754.

- Zickler D and Kleckner N (1998) The leptotene-zygotene transition of meiosis. Annu. Rev. Genet. 32, 619-697.

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