Mécanismes moléculaires de la dynamique des chromosomes

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Daniele Fachinetti

Fachinetti

Daniele Fachinetti Chef d'équipe Equipe Fachinetti CR1 CNRS Tél :

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"I performed my PhD work with Marco Foiani (IFOM, Italy) where I identified for the first time the sites where DNA replicationtermination occurs, and the molecular mechanisms behind this process (Fachinetti et al., 2010). The study of replication fragile zones sparked my interest in centromeres, which led to my move in 2010 to the laboratory of Don W. Cleveland at the Ludwig Institute in the University of California, San Diego (UCSD). As post-doc, I have characterized a system for rapid protein degradation in human cells, the Auxin-mediated degradation (Holland, Fachinetti et al., 2012). I then combined genome-editing techniques to answer to two long-standing questions in genetics: the nature of the epigenetic mark of centromeres (Fachinetti et al., 2013; Fachinetti et al., 2017) and the role of centromeric DNA sequence in centromere function (Fachinetti et al., 2015). These findings open new routes of investigation necessary for our understanding of centromere establishment and function and overall the maintenance of genome stability. I then started as a group leader at the “Department of cell biology and cancer” at the Institut Curie supported by the ATIP-AVENIR program in 2016.

My team is now studying what we think are the most pressing questions in chromosome biology: 1) Genetic and epigenetic mechanisms that control faithful transmission of our genetic material; 2) DNA architecture of certain chromosomal regions such as centromeres; 3) Identification of the key enzymes protecting the integrity of our genome. We use molecular and cell biology approaches combined with genetics, physics and biochemistry."

Publications clés

Année de publication : 2020

Sebastian Hoffmann, Helena M Izquierdo, Riccardo Gamba, Florian Chardon, Marie Dumont, Veer Keizer, Solène Hervé, Shannon M McNulty, Beth A Sullivan, Nicolas Manel, Daniele Fachinetti (2020 Sep 18)

A genetic memory initiates the epigenetic loop necessary to preserve centromere position.

The EMBO journal : e105505 : DOI : 10.15252/embj.2020105505

Année de publication : 2019

Marie Dumont, Riccardo Gamba, Pierre Gestraud, Sjoerd Klaasen, Joseph T Worrall, Sippe G De Vries, Vincent Boudreau, Catalina Salinas-Luypaert, Paul S Maddox, Susanne Ma Lens, Geert Jpl Kops, Sarah E McClelland, Karen H Miga, Daniele Fachinetti (2019 Nov 22)

Human chromosome-specific aneuploidy is influenced by DNA-dependent centromeric features.

The EMBO journal : e102924 : DOI : 10.15252/embj.2019102924
Simon Gemble, Anthony Simon, Carole Pennetier, Marie Dumont, Solène Hervé, Franz Meitinger, Karen Oegema, Raphaël Rodriguez, Geneviève Almouzni, Daniele Fachinetti, Renata Basto (2019 Sep 10)

Centromere Dysfunction Compromises Mitotic Spindle Pole Integrity.

Current biology : CB : 3072-3080.e5 : DOI : S0960-9822(19)30932-7
Andrea Scelfo, Daniele Fachinetti (2019 Aug 21)

Keeping the Centromere under Control: A Promising Role for DNA Methylation.

Cells : DOI : E912
Viviana Barra, Glennis A Logsdon, Andrea Scelfo, Sebastian Hoffmann, Solène Hervé, Aaron Aslanian, Yael Nechemia-Arbely, Don W Cleveland, Ben E Black, Daniele Fachinetti (2019 Jan 13)

Phosphorylation of CENP-A on serine 7 does not control centromere function.

Nature communications : 175 : DOI : 10.1038/s41467-018-08073-1

Année de publication : 2018

V Barra, D Fachinetti (2018 Oct 20)

The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA.

Nature communications : 4340 : DOI : 10.1038/s41467-018-06545-y

Année de publication : 2017

Fachinetti D, Logsdon GA, Abdullah A, Selzer EB, Cleveland DW, Black BE (2017 Jan 9)

CENP-A Modifications on Ser68 and Lys124 Are Dispensable for Establishment, Maintenance, and Long-Term Function of Human Centromeres.

Dev Cell : 40 : 104-113 : DOI : 10.1016/j.devcel.2016.12.014

Année de publication : 2016

Sebastian Hoffmann, Marie Dumont, Viviana Barra, Peter Ly, Yael Nechemia-Arbely, Moira A McMahon, Solène Hervé, Don W Cleveland, Daniele Fachinetti (2016 Nov 24)

CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly.

Cell reports : 2394-2404 : DOI : 10.1016/j.celrep.2016.10.084

Année de publication : 2015

Daniele Fachinetti, Joo Seok Han, Moira A McMahon, Peter Ly, Amira Abdullah, Alex J Wong, Don W Cleveland (2015 May 4)

DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere Function.

Developmental cell : 314-27 : DOI : 10.1016/j.devcel.2015.03.020

Année de publication : 2013

Daniele Fachinetti, H Diego Folco, Yael Nechemia-Arbely, Luis P Valente, Kristen Nguyen, Alex J Wong, Quan Zhu, Andrew J Holland, Arshad Desai, Lars E T Jansen, Don W Cleveland (2013 Feb 7)

A two-step mechanism for epigenetic specification of centromere identity and function.

Nature cell biology : 1056-66 : DOI : 10.1038/ncb2805

Année de publication : 2012

Andrew J Holland, Daniele Fachinetti, Joo Seok Han, Don W Cleveland (2012 Nov 12)

Inducible, reversible system for the rapid and complete degradation of proteins in mammalian cells.

Proceedings of the National Academy of Sciences of the United States of America : E3350-7 : DOI : 10.1073/pnas.1216880109
Yael Nechemia-Arbely, Daniele Fachinetti, Don W Cleveland (2012 Mar 23)

Replicating centromeric chromatin: spatial and temporal control of CENP-A assembly.

Experimental cell research : 1353-60 : DOI : 10.1016/j.yexcr.2012.04.007

Année de publication : 2010

Daniele Fachinetti, Rodrigo Bermejo, Andrea Cocito, Simone Minardi, Yuki Katou, Yutaka Kanoh, Katsuhiko Shirahige, Anna Azvolinsky, Virginia A Zakian, Marco Foiani (2010 Feb 23)

Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements.

Molecular cell : 595-605 : DOI : 10.1016/j.molcel.2010.07.024