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Accueil > Départements > Biologie des Génomes > Laure CRABBE : Telomeres et organisation du génome

Les publications


  • T. Candelli, D. Challal, J. - B. Briand, J. Boulay, O. Porrua, J. Colin, et D. Libri, « High-resolution transcription maps reveal the widespread impact of roadblock termination in yeast », The EMBO journal, janv. 2018.
    Résumé : Transcription termination delimits transcription units but also plays important roles in limiting pervasive transcription. We have previously shown that transcription termination occurs when elongating RNA polymerase II (RNAPII) collides with the DNA-bound general transcription factor Reb1. We demonstrate here that many different DNA-binding proteins can induce termination by a similar roadblock (RB) mechanism. We generated high-resolution transcription maps by the direct detection of RNAPII upon nuclear depletion of two essential RB factors or when the canonical termination pathways for coding and non-coding RNAs are defective. We show that RB termination occurs genomewide and functions independently of (and redundantly with) the main transcription termination pathways. We provide evidence that transcriptional readthrough at canonical terminators is a significant source of pervasive transcription, which is controlled to a large extent by RB termination. Finally, we demonstrate the occurrence of RB termination around centromeres and tRNA genes, which we suggest shields these regions from RNAPII to preserve their functional integrity.
    Mots-clés : BDG, DBG, pervasive transcription, Rap1, roadblock termination, TENOR, transcription readthrough, transcription termination mechanism.


  • E. Krzywinska, C. Kantari-Mimoun, Y. Kerdiles, M. Sobecki, T. Isagawa, D. Gotthardt, M. Castells, J. Haubold, C. Millien, T. Viel, B. Tavitian, N. Takeda, J. Fandrey, E. Vivier, V. Sexl, et C. Stockmann, « Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis », Nature Communications, vol. 8, nᵒ 1, p. 1597, nov. 2017.
    Résumé : Productive angiogenesis, a prerequisite for tumour growth, depends on the balanced release of angiogenic and angiostatic factors by different cell types within hypoxic tumours. Natural killer (NK) cells kill cancer cells and infiltrate hypoxic tumour areas. Cellular adaptation to low oxygen is mediated by Hypoxia-inducible factors (HIFs). We found that deletion of HIF-1α in NK cells inhibited tumour growth despite impaired tumour cell killing. Tumours developing in these conditions were characterised by a high-density network of immature vessels, severe haemorrhage, increased hypoxia, and facilitated metastasis due to non-productive angiogenesis. Loss of HIF-1α in NK cells increased the bioavailability of the major angiogenic cytokine vascular endothelial growth factor (VEGF) by decreasing the infiltration of NK cells that express angiostatic soluble VEGFR-1. In summary, this identifies the hypoxic response in NK cells as an inhibitor of VEGF-driven angiogenesis, yet, this promotes tumour growth by allowing the formation of functionally improved vessels.
    Mots-clés : DBG, TENOR.


  • B. Pardo, L. Crabbé, et P. Pasero, « Signaling Pathways of Replication Stress in Yeast », FEMS yeast research, déc. 2016.
    Résumé : Eukaryotic cells activate the S-phase checkpoint in response to a variety of events affecting the progression of replication forks, collectively referred to as replication stress. This signaling pathway is divided in two branches: the DNA damage checkpoint (DDC) and the DNA replication checkpoint (DRC). Both pathways are activated by the sensor kinase Mec1 and converge on the effector kinase Rad53. However, the DDC operates throughout the cell cycle and depends on the checkpoint mediator Rad9 to activate Rad53, whereas the DRC is specific to S phase and is mediated by Mrc1 and other fork components to signal replication impediments. In this review, we summarize current knowledge on these two pathways, with a focus on the budding yeast Saccharomyces cerevisiae, in which many important aspects of the replication stress response were discovered. We also discuss the differences and similarities between DDC and DRC and speculate on how these pathways cooperate to ensure the complete and faithful duplication of the yeast genome under various replication stress conditions.
    Mots-clés : DBG, TENOR.
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Publications majeures avant 2015

- Cesare A. J., Hayashi, M.T., Crabbe L., Karlseder J. (2013) The telomere deprotection is functionally distinct from the genomic DNA damage response. Molecular Cell 25(2):141-55

- Crabbe L., Cesare A. J., Kasuboski J. M., Fitzpatrick J. A. J., Karlseder J. (2012) Human telomeres are tethered to the nuclear periphery during post-mitotic nuclear assembly. Cell Reports 2(6):1521-9

- Crabbe L., Karlseder J. (2010). Mammalian Rap1 widens its impact. Nature Cell Biology 12(8):733-5

- Crabbe L., Jauch A., Naeger C.M., Holtgreve-Grez H., Karlseder J. (2007). Telomere dysfunction as a cause of genomic instability in Werner Syndrome. Proc Natl Acad Sci USA 104(7):2205-10

- Crabbe L., Verdun R.E., Haggblom C.I., Karlseder J. (2004). Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306(5703):1951-3.

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