Yeast Molecular Genetics - CNRS (URA2171) and Univ. P. M. Curie (UFR927)  


  HEADProf. DUJON Bernard / bdujon@pasteur.fr
  MEMBERSDr CHATRE Laurent* / CHAYOT Romain* / Dr FABRE Emmanuelle / Dr FAIRHEAD Cécile / Dr FISCHER Gilles / Dr KOSZUL Romain / Dr LAFONTAINE Ingrid / MONTAGNE Benjamin* / Dr OZIER-KALOGEROPOULOS Odile / PAYEN Célia / RAMBAUD Martine / Dr RICHARD Guy-Franck / Dr RICCHETTI Miria* / ROLLAND Thomas / Dr SACERDOT Christine / TEKAIA Fredj / THERIZOLS Pierre / THIERRY Agnès
* associated team working on replication and mitochondrial DNA transfer in mammalian cells.


  Annual Report

The Unité has contributed to the early genome sequencing of the baker’s yeast Saccharomyces cerevisiae, back in 1996, and to the considerable development of functional genomics since then. It has also initiated the first large-scale comparative genomic study of hemiascomycetes (budding yeasts), in collaboration with five other french laboratories (the Génolevures Consortium), the CNS-Génoscope and the Génopole Pasteur-Ile de France. The originality of the Unité relies on the combination of experimental approaches, performed on S. cerevisiae and few other species, to study the molecular mechanisms of genome evolution, and comparative genomic approaches on many yeast species to generate experimentally testable hypotheses.

Comparative genomics of hemiascomycetous yeasts and the mechanisms of eukaryotic genome evolution.

The hemiascomycetous yeasts, a large subdivision of the fungal kingdom, cover a much broader evolutionary range than anticipated from their morphological and biological similarities. The Génolevures Consortium has sequenced and annotated eight species, representative of different and distant branches of hemiascomycetes (http://www.genolevures.org). One of them, Candida glabrata, is a human pathogen. The comparisons of genes and their products as well as genome maps and chromosomal organization between the sequenced species revealed important mechanisms of eukaryotic genome evolution. Special attention was given to gene duplication and loss, horizontal gene transfer, long sequence repeats, genes involved in sex, replication, recombination or repair mechanisms, as well as tRNA genes, subtelomeric regions, mitochondrial genomes and insertion of their fragments into nuclear chromosomes.

Chromosome dynamics, nuclear architecture and their functional and evolutionary consequences.

A novel, replication-based mechanism was identified in S. cerevisiae as responsible for the spontaneous formation of large segmental duplications, similar to those observed in human that play a role in genome instability and evolution. Similarly, the role of chromosome breaks and recombination for the stability of triplet repeats in eukaryotic genomes was determined using S. cerevisiae mutants. The spatial distribution of subtelomeres around the nuclear periphery, hence their possible interactions, was measured quantitatively by fluorescence microscopy of living cells in wild-type and mutants strains of S. cerevisiae. Several causes were identified for the lack of sexuality of C. glabrata, a frequent feature for fungal pathogens, and the corresponding effects on its population structure and polymorphism were analyzed by molecular methods.

Keywords: Génomique, Evolution, Instabilités génétiques, Noyau, Réplication, Analyse des séquences

Gmlev.jpg

Scheme of replication factory interactions forming spontaneously arising segmental duplications during genome evolution



  Publications

P. THERIZOLS, C. FAIRHEAD, G. C. CABAL, A. GENOVESIO, J-C. OLIVO-MARIN, B. DUJON, E. FABRE (2006)
Telomere tethering at the nuclear periphery is essential for efficient DNA double-strand break repair in subtelomeric region.
J. Cell Biol. 172: 189-199

B. DUJON (2006)
Yeasts illustrate the molecular mechanisms of eukaryotic genome evolution.
Trends in Genetics 22: 375-387

C. PAYEN, R. KOSZUL, B. DUJON, G. FISCHER (2008)
Segmental duplications arise from PoI32-dependent repair of broken forks through two alternative replication-based mechanisms.
PloS Genetics 4(9) e1000175

A. THIERRY, C. BOUCHIER, B. DUJON, G-F. RICHARD (2008)
Megasatellites: a peculiar class of giant minisatellites in genes involved in cell adhesion and pathogenicity in Candida glabrata.
Nuc. Acids Res. 36: 5970-5982

H. MULLER, C. HENNEQUIN, J. GALLAUD, B. DUJON, C. FAIRHEAD. (2008)
The asexual yeast Candida glabrata maintains distinct a and alpha haploid mating types. Eukaryotic Cell 7: 848-858.



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Activity Reports 2009 - Institut Pasteur
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