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    Welcome to the “Epigenetics, DNA replication and Cancer” group!

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    We are very excited to announce that three junior teams will move to Institute Cochin in the next months. The group, led by Benoit Miotto, is already settling down in the department “Development, Reproduction and Cancer” at the faculty building. Benoit and his co-workers focus on the development of bioinformatics, molecular and cellular assays to better characterize the pathways and enzymes involved in the control of DNA replication in human, with a focus on epigenetic regulators and chromatin marks.

     The objective of the group is to discover new mechanisms in the control of DNA replication and to understand how deregulation of these mechanisms may contribute to genomic instability in cancer.

     

    Main contributions include:

    • Chromatin plays a key role in the control of the activity of origins of replication. A fine tuning of histone marks dynamics at origins orchestrates the assembly onto the DNA of the pre-replication complex and other DNA replication initiation factors (Miotto et Struhl, 2008, 2010; Benatti et al., 2015). These regulations may also ensure that origins are activated once and only once per cell cycle (Miotto et Struhl, 2010; Suchyta et al., 2015).
    • Alterations of the spatiotemporal program of DNA replication may explain specific chromosomal rearrangements detected in cancer. The group identified a new pathway, comprised of an E3 ligase RBBP6 and a methyl-DNA binding protein ZBTB38, regulating common fragile site replication and stability. Inactivation of RBBP6 causes accumulation of ZBTB38 protein and breaks at common fragile site because of delayed replication of these regions (Miotto et al., 2014).
    • Development of new protocols and bioinformatics tools to study the assembly of the pre-replication complex and the program of DNA replication at the genome scale (Miotto et al., submitted).

     

    Dr Miotto’s Team is supported by Institut Cochin, by the laboratory of excellence “Who am I?” (http://www.labex-whoami.org/fr/presentation) and by the Fondation pour la Recherche Médicale (https://www.frm.org/).

    For a more detailed description of the work, please see the web page of the team

     

    Legend: from left to right: Claire Marchal, Samia Oussous,
    Benjamin Martin, Nadège Guinot and Benoit Miotto.

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