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Mobile elements, integrity and plasticity of the human genome


This team does no longer belong to IGH since 01-01-2015

(Department Genome Dynamics)

 

Leader: Nicolas GILBERT

 

Interspersed repeat sequences are present in almost all eukaryotic genomes. The LINE-1 (Long Interspersed Element-1 or L1) retrotransposon is the most abundant mobile element of the human genome. Approximately 500,000 copies of L1 represent ~17% of human DNA. The vast majority of these copies are considered as molecular fossils. However, ~100 elements remain potentially active (RC-L1). Because of their activity L1 can induce genetic diseases by insertional mutation in either coding or regulatory regions. Moreover, because of its high representation in the genome, L1 can generate deleterious genomic rearrangements induced by non allelic homologous recombination.

Although L1 mobility can induce genetic instability, the mechanism of L1 retrotransposition is still poorly understood. Our team focuses on the understanding of the molecular mechanisms of L1 transposition and its impact on the genome. We are particularly interested in the L1 ribonucleoprotein complex formation, intermediate of retrotransposition. We also would like to understand the interplay between DNA repair mechanisms and the resolution of L1 insertion. We use two complementary approaches. First, we utilize a cell cultured assay that allows us to control L1 retrotransposition. It will help us to decorticate the different steps of L1 retrotransposition. Second, we perform in silico analyses to support our molecular approach and to reveal the L1 implication in genomic variability and evolution of mammalian genomes.

 

 

 

 

The 2 lastest publications of the group:

Doucet, A.J., Droc, G., Siol, O., Audoux, J., Gilbert, N..
U6 snRNA pseudogenes: markers of retrotransposition dynamics in mammals
(2015), Mol Biol Evol : 32(7):1815-32
Schmith A, Groth M, Ratka J, Gatz S, Spaller T, Siol O, Glöckner G, Winckler T..
Conserved gene-regulatory function of the carboxy-terminal domain of dictyostelid C-module-binding factor
(2013), Eukaryot Cell. : 12, 3, 460-468

 

All the publications of the group

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  INSTITUTE of HUMAN GENETICS
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  Montpellier, France