Metazoan nuclear pore complexes in gene regulation and genome stability.
Nobari P, Doye V, Boumendil C
Nuclear architecture in physiology and pathology
In eukaryotic cells, the genetic material - the DNA, stored in the nucleus is facing two major challenges: (i) there are different subcompartments in the nucleus (ii) it is organized as a nucleo-protein complex in the form of chromatin. These two levels can potentially contribute to modulate all genome functions.
Our lab is interested in understanding how these two levels of nuclear architecture (nuclear compartments and chromatin organization) cooperate to allow the regulation of DNA functions such as DNA repair or gene expression. As an example, while the nuclear lamina usually associates with compact chromatin, called heterochromatin, the nuclear pores are always devoid of heterochromatin association. We recently showed that nuclear pores density increase can trigger major chromatin rearrangements during cellular senescence, which correlates with the expression of a specific inflammatory gene network.
We use a variety of approaches including cellular and molecular biology, advanced imaging methods and synthetic biology in various cellular models, including cellular senescence and mouse embryonic stem cells.
More specifically the questions we currently ask in the lab are:
- How the physical properties of the nuclear pores compartments participate in chromatin organization?
- What is the role of nuclear pores density and composition in the definition of cellular identity?
- How chromatin reorganization at the global scale influences gene expression during cellular senescence?
Figure 1- The nuclear pores and the nuclear lamina are two distinct nuclear compartments forming the nuclear envelope. While the nuclear lamina associates with compact heterochromatin, the nuclear pores are always devoid of heterochromatin association.
Publications of the team
Cornelia de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect
Gabrielle Olley, Madapura M. Pradeepa, Graeme R. Grimes, Sandra Piquet, Sophie E. Polo, David R. FitzPatrick, Wendy A. Bickmore, Charlene Boumendil
Expression of progerin does not result in an increased mutation rate.
Deniaud E, Lemaître C, Boyle S, Bickmore WA
Chromatin at the nuclear periphery and the regulation of genome functions.
Lemaître C, Bickmore WA
DSB (Im)mobility and DNA repair compartmentalization in mammalian cells.
Lemaître C, Soutoglou E
Nuclear position dictates DNA repair pathway choice.
Lemaître C, Grabarz A, Tsouroula K, Andronov L, Furst A, Pankotai T, Heyer V, Rogier M, Attwood KM, Kessler P, Dellaire G, Klaholz B, Reina-San-Martin B, Soutoglou E
Disruption of TTDA results in complete nucleotide excision repair deficiency and embryonic lethality.
Theil AF, Nonnekens J, Steurer B, Mari PO, de Wit J, Lemaitre C, Marteijn JA, Raams A, Maas A, Vermeij M, Essers J, Hoeijmakers JH, Giglia-Mari G, Vermeulen W
The nucleoporin 153, a novel factor in double-strand break repair and DNA damage response
C Lemaître, B Fischer, A Kalousi, A-S Hoffbeck, J Guirouilh-Barbat, O D Shahar, D Genet, M Goldberg, P Betrand, B Lopez, L Brino & E Soutoglou
Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in breast cancer.
Corpet A, De Koning L, Toedling J, Savignoni A, Berger F, Lemaître C, O\'Sullivan RJ, Karlseder J, Barillot E, Asselain B, Sastre-Garau X, Almouzni G
Heterochromatin protein 1alpha: a hallmark of cell proliferation relevant to clinical oncology.
De Koning L, Savignoni A, Boumendil C, Rehman H, Asselain B, Sastre-Garau X, Almouzni G
DNA damage response in the absence of DNA lesions continued...
Pankotai T, Hoffbeck AS, Boumendil C, Soutoglou E