The student will be working in the Biology of repetitive sequences lab, under the supervision of Jerome DEJARDIN. Website: https: // www. igh.cnrs.fr/en/research/departments/genome- dynamics/biologie...
Mammalian telomeres are composed of a tandem array of specific DNA motifs, to which a dedicated set of factors named shelterin proteins specifically bind. Shelterin proteins regulate telomere replication, their length control and critically, their protection. Telomere Repeat binding Factor 2 (TRF2) is a shelterin which specifically binds to telomeric DNA. TRF2 is involved in the formation of the telomere-loop (T-loop), a crucial terminal structure in which the single stranded telomere DNA overhang stably invades the duplex telomeric DNA. This structure prevents telomeres from being recognized as mere double strand breaks and aberrantly fused by non-homologous end-joining activities. Thus, in the absence of TRF2, telomeres become the substrate of DNA repair activities which lead to spectacular “trains” of chromosome fused through their telomeres. How TRF2 enforces T-loop formation is only partly understood, but TRF2 is viewed as a central telomere component required to protect telomeres in all tissues. Yet, recent work has demonstrated that TRF2, while present on telomeres, is dispensable for telomere protection and T-loop formation in embryonic stem cells and earlier pre-implantation stages. This surprising result suggests that other factors/mechanisms are involved in telomere protection in these contexts. We have identified a previously uncharacterized protein which binds telomeres in early embryos. In the absence of TRF2, the loss of this protein leads to strong DNA damage response at telomeres and telomere fusions. We propose to study the function of this protein with in vivo as well as in vivo approaches. As telomeres are key controllers of the replicative potential of cells and of chromosome stability, it is central to understand the mechanistic underpinnings of their protection, as this could lead to advances in cancer or anti-aging therapy.Additional comments
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https: // emploi.cnrs.fr/Offres/Doctorant/UMR9002-JERDEJ-004/Default.aspxRequired Research Experiences
Biological sciences › Biology
Biological sciences: Master Degree or equivalent
FRENCH: BasicContact Information