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Programmed genome rearrangements: mechanisms and regulation

Team leader: 
Mireille Betermier
Team members: 
Julien Bischerour
Emeline Dubois
Antoine Marmignon
Nathalie Mathy
Vinciane Regnier
Institute or University: 
CNRS - Centre de Genetique Moleculaire
CNRS UPR3404
1 avenue de la Terrasse
Gif-sur-Yvette
91190
France
Research interests: 

We use the ciliate Paramecium tetraurelia as a model to unravel the mechanisms involved in the introduction of programmed DSBs and their repair. In this unicellular eukaryote, extensive genome rearrangements take place at each sexual cycle, during development of the somatic nucleus. In particular, thousands of short non-coding sequences (IES or internal eliminated sequences) are spliced out from somatic chromosomes. We discovered that IES excision is initiated by DSBs that depend on a domesticated transposase (PiggyMac or Pgm) and that the NHEJ pathway repairs IES excision sites following highly controlled processing of Pgm-dependent DSBs. Because numerous genes in the germline are interrupted by at least one IES, efficient and precise excision is essential, making Paramecium a powerful model for the study of programmed genome rearrangements. Our research focuses on three aspects: (i) the structure-function analysis of Pgm, (ii) the search for genetic and epigenetic determinants that target Pgm to its cleavage sites and (iii) the study of the factors that couple DNA cleavage to precise DSB repair.Our team is activately participating in the effort of the Paramecium community to provide deeper insight into the structure and organization of the somatic and germline genomes of Paramecium tetraurelia.

Keywords: 
DNA double-strand break
domesticated transposase
DNA repair
non-homologous end joining
transposons
IES
Techniques: 
molecular biology of DNA and RNA
protein purification
Publications: 

 

  1. Arnaiz, O., Mathy, N., Baudry, C., Malinsky, S., Aury, J.M., Denby-Wilkes, C., Garnier, O., Labadie, K., Lauderdale, B., Le Mouël, A., Marmignon, A., Nowacki, M., Poulain, J., Prajer, M., Wincker, P., Meyer, E., Duharcourt, S., Duret, L., Bétermier, M.*, Sperling, L.* (2012) The Paramecium germline genome provides a niche for intragenic parasitic DNA: Evolutionary Dynamics of Internal Eliminated Sequences. PloS Genet.. 8(10):e1002984. Epub 2012 Oct 4. *co-corresponding authors.
  2. Dubois, E., Bischerour, J., Marmignon, A., Mathy, N., Régnier, V., Bétermier, M. (2012) Transposon invasion of the Paramecium germline genome countered by a domesticated PiggyBac transposase and the NHEJ pathway. International Journal of Evolutionary Biology. 2012:436196. Epub 2012 Jul 22.
  3. Kapusta, A.*, Matsuda, A.*, Marmignon, A., Ku, M., Silve, A., Meyer, E., Forney, J.D., Malinsky, S., Bétermier, M. (2011) Highly precise and developmentally programmed genome assembly in Paramecium requires Ligase IV-dependent end joining. PloS Genet. 7(4) :e1002049. Epub 2011 Apr 14.
  4. Nowak, J.K., Gromadka, R., Juszczuk, M., Jerka-Dziadosz, M., Maliszewska, K., Mucchielli, M.H., Gout, J.F., Arnaiz, O., Agier, N., Tang, T., Aggerbeck, L.P., Cohen, J., Delacroix, H., Sperling, L., Herbert, C.J., Zagulski, M., Bétermier, M. (2011) A functional study of genes essential for autogamy and nuclear reorganization in Paramecium. Eukaryot. Cell. 10(3) :363-372.
  5. Bouchouche, K., Gout, J.F., Kapusta, A., Bétermier, M., Meyer, E. (2011) Functional specialization of Piwi proteins in Paramecium tetraurelia from post-transcriptional gene silencing to genome remodelling. Nucl. Acids Res. 39(10) :4249-4264. Epub 2011 Jan 7.
  6. Arnaiz, O., Gout, J.F., Bétermier, M., Bouhouche, K., Cohen, J., Duret, L., Kapusta, A., Meyer, E., Sperling, L. (2010) Gene expression in a paleopolyploid: a transcriptome resource for the ciliate Paramecium tetraurelia. BMC Genomics 11 :547.
  7. Beisson, J., Bétermier, M., Bré, M-H., Cohen, J., Duharcourt, S., Duret, L., Kung, C., Malinsky, S., Meyer, E., Preer Jr, J. R., Sperling, L. (2010). Paramecium tetraurelia: The Renaissance of an Early Unicellular Model. In « Emerging Model Organisms ». Cold Spring Harbor Protocols. 2010 (1) : doi:10.1101/pdb.emo140.
  8. Baudry, C.*, Malinsky, S.*, Restituito, M., Kapusta, A., Rosa, S., Meyer, E., Bétermier, M. (2009) PiggyMac, a domesticated piggyBac transposase involved in programmed genome rearrangements in the ciliate Paramecium tetraurelia. Genes & Dev. 23 : 2478-2483.
  9. Lepère, G., Bétermier, M., Meyer, E., Duharcourt, S. (2008) Maternal noncoding transcripts antagonize the targeting of DNA elimination by scanRNAs in Paramecium tetraurelia. Genes & Dev. 22 :1501-1512.
  10. Gratias, A., Lepère, G., Garnier, O., Rosa, S., Duharcourt, S., Malinsky, S., Meyer, E., Bétermier, M. (2008) Developmentally programmed DNA splicing in Paramecium reveals short-distance crosstalk between DNA cleavage sites. Nucl. Acids Res. 36 :3244-3251.
  11. Duret, L., Cohen, J., Jubin, C., Dessen, P., Goût, J.F., Mousset, S., Aury, J.M., Jaillon, O., Noël, B., Arnaiz, O., Bétermier, M., Wincker, P., Meyer, E., Sperling, L. (2008) Analysis of sequence variability in the macronuclear DNA of Paramecium tetraurelia: a somatic view of the germ line. Genome Res. 18 :585-596.
  12. Jaillon, O.*, Bouhouch, K.*, Gout, J.F., Aury, J.M., Noël, B., Saudemont, B., Nowacki, M. Serrano, V., Porcel, B.M., Ségurens, B., Le Mouël, A., Lepère, G., Schächter, V., Bétermier, M., Cohen, J., Wincker, P., Sperling, L., Duret, L. and Meyer, E. (2008) Translational Control of Intron Splicing in Eukaryotes. Nature 451 :359-363.
  13. Aury, J.M., Jaillon, O., Duret, L., Noel, B., Jubin, C., Porcel, B.M., Segurens, B., Daubin, V., Anthouard, V., Aiach, N., Arnaiz, O., Billaut, A., Beisson, J., Blanc, I., Bouhouche, K., Camara, F., Duharcourt, S., Guigo, R., Gogendeau, D., Katinka, M., Keller, A.M., Kissmehl, R., Klotz, C., Koll, F., Le Mouel, A., Lepere, G., Malinsky, S., Nowacki, M., Nowak, J.K., Plattner, H., Poulain, J., Ruiz, F., Serrano, V., Zagulski, M., Dessen, P., Bétermier, M., Weissenbach, J., Scarpelli, C., Schachter, V., Sperling, L., Meyer, E., Cohen, J., Wincker, P. (2006) Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia. Nature 444 :171-178.
  14. Bétermier, M. (2004). Large-scale genome remodelling by the developmentally programmed elimination of germ line sequences in the ciliate Paramecium. Res. Microbiol. 155 : 399-408.
  15. Gratias, A., Bétermier, M. (2003) Processing of double-strand breaks is involved in the precise excision of Paramecium IESs. Mol. Cell. Biol. 23 : 7152-7162.
  16. Dessen, P., Zagulski, M., Gromadka, R., Plattner, H., Kissmehl, R., Meyer, E., Bétermier, M., Schultz, J.E., Linder, J.U., Pearlman, R.E., Kung, C., Forney, J., Satir, B., van Houten, J.L., Keller, A.M., Froissard, M., Sperling, L., Cohen, J. (2001) Paramecium genome survey : a pilot project. Trends Genet. 17 : 306-308.
  17. Gratias, A., Bétermier, M. (2001). Developmentally programmed excision of internal DNA sequences in Paramecium aurelia. Biochimie. 83 : 1009-1022.
  18. Bétermier, M., Duharcourt, S., Seitz, H., Meyer, E. (2000) Timing of developmentally programmed excision and circularization of Paramecium internal eliminated sequences. Mol. Cell. Biol. 20 : 1553-1561.

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