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    Epigenetics, DNA replication and Cancer

    Team leader

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    The laboratory integrates genomics, molecular biology and cell biology to gain insight into the regulation of DNA replication in human. We are particularly interested in understanding how the DNA replication machinery is assembled in the context of chromatin and in characterizing the mechanisms and pathways regulating the initiation of DNA replication. Since many of these regulatory pathways are deregulated in cancer, our studies will help understand how normal and cancer cells regulate DNA replication.

     

    Objectives

    The interest of the group is to better understand the regulation of DNA replication initiation in mammals. Notably, we are developing studies to identify and to characterize new mechanisms in the initiation of DNA replication in vivo. Using biochemical, genetic and genomic approaches we are studying the role of signaling pathways, chromatin factors and chromatin-dynamics in defining the position of origins of replication, and in regulating the initiation of DNA replication. We use a number of different model systems to study these mechanisms (human primary cells, stem cells, cancer cells).

    Specific research interests :

    • How is DNA replication initiation regulated (notably by chromatin)?
    • How is DNA replication coordinated with other nuclear processes?
    • How is DNA replication dysregulated in cancer (and other human pathologies)?
    • How is dysregulation of DNA replication contributing to genomic instability and disease progression?


    Keywords : Epigenetics, DNA replication, Genome stability, Cancer

     

    Main publications

    • Fernandes P, Miotto B, Saint-Ruf C, Said M, Barra V, Nähse V, Ravera S, Cappelli E, Naim V. FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability. Commun Biol. 2021 Jan 29;4(1):127.
    • De Dieuleveult M, Marchal C, Jouinot A, Letessier A, Miotto B. Molecular and clinical relevance of ZBTB38 expression levels in prostate cancer. Cancers (Basel). 2020 Apr 29; 12(5).
    • Miotto B, Marchal C, Adelmant G, Guinot N, Xie P, Marto JA, Zhang L, Defossez PA. Stabilization of the methyl-CpG binding protein ZBTB38 by the deubiquitinase USP9X limits the occurrence and toxicity of oxidative stress in human cells. Nucleic Acids Res. 2018 May 18;46(9):4392-4404.
    • Miotto B, Ji Z, Struhl K. (2016) Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers. Proc Natl Acad Sci U S A. Aug 16;113(33):E4810-9.
    • Miotto B., Chibi M., Xie P., Koundrioukoff S., Moolan-Smook H., Pugh D., He F., Debatisse M., Zhang L. and Defossez P.A. The RBBP6/ZBTB38/MCM10 axis regulates DNA replication and common fragile site stability. Cell Reports 2014 S2211
    • Miotto B. and Struhl K. (2011) JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress. Mol. Cell 44(1) 62-71.

     

    Team's news

    • New BioRxiv publications on stem cells (here) and DNA hydroxymethylation (here)
    • New publications in Environmental Research (here) and Communications Biology (here).
    • Welcome to Manon Watzky. New PhD student! (2019)
    • Congratulations to Maud de Dieuleveult. Post-doctoral grant application selected by Labex « Who am I ? » (2019)
    • Selected « Amorçage 2015 » by Fondation pour la Recherche Médicale.
    • Selected « Emerging Team 2015 » by Labex « Who am I ? ».

     

    Contact

    Students and post-doctoral applications are evaluated on a continuing basis. Candidates wishing to visit the laboratory should contact Dr for further information.

     

    Financial Supports