UMR3244 – Dynamics of Genetic Information

Teams in this unit aim at elucidating the regulation of mechanisms that are crucial to the maintenance of genome integrity, like DNA replication, repair and recombination, as well as the role of cell cycle checkpoints and non-coding RNAs in genome and epigenome maintenance.

Experimental models include yeast, mammalian and human cell lines, mutant mouse models and tumour samples. A large variety of methods is used including genetic, molecular and cytogenetic techniques, fluorescence in situ hybridisation and DNA ‘combing’, as well as high throughput sequencing approaches such as DNA-seq for mutation landscape analyses, RNA-seq for transcriptome analyses and ChIP-seq mapping of chromatin-associated proteins and their genome-wide modulation in response to DNA damages.

 

Key publications

Year of publication 2020

Gnan Stefano, Liu Yaqun, Spagnuolo Manuela, Chen Chun-Long (2020 Aug 31)

The impact of transcription-mediated replication stress on genome instability and human disease

Genome Instability & Disease : 1 : 207-234 : DOI : 10.1007/s42764-020-00021-y
Elda Cannavo, Aurore Sanchez, Roopesh Anand, Lepakshi Ranjha, Jannik Hugener, Céline Adam, Ananya Acharya, Nicolas Weyland, Xavier Aran-Guiu, Jean-Baptiste Charbonnier, Eva R Hoffmann, Valérie Borde, Joao Matos, Petr Cejka (2020 Aug 21)

Regulation of the MLH1-MLH3 endonuclease in meiosis.

Nature : DOI : 10.1038/s41586-020-2592-2
Alexy Promonet, Ismaël Padioleau, Yaqun Liu, Lionel Sanz, Anna Biernacka, Anne-Lyne Schmitz, Magdalena Skrzypczak, Amélie Sarrazin, Clément Mettling, Maga Rowicka, Krzysztof Ginalski, Frédéric Chedin, Chun-Long Chen, Yea-Lih Lin, Philippe Pasero (2020 Aug 10)

Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites.

Nature communications : 3940 : DOI : 10.1038/s41467-020-17858-2
Eléonore Toufektchan, Vincent Lejour, Romane Durand, Neelam Giri, Irena Draskovic, Boris Bardot, Pierre Laplante, Sara Jaber, Blanche P Alter, José-Arturo Londono-Vallejo, Sharon A Savage, Franck Toledo (2020 Apr 18)

Germline mutation of MDM4, a major p53 regulator, in a familial syndrome of defective telomere maintenance.

Science advances : eaay3511 : DOI : 10.1126/sciadv.aay3511
Franck Toledo and Michelle Debatisse (2020 Apr 17)

Mechanisms generating cancer genome complexity : a look back at the interphase breakage model

Science : Vol. 368, Issue 6488 : eaba0712 : DOI : 10.1126/science.aba0712

Year of publication 2019

Olivier Brison, Sami El-Hilali, Dana Azar, Stéphane Koundrioukoff, Mélanie Schmidt, Viola Nähse, Yan Jaszczyszyn, Anne-Marie Lachages, Bernard Dutrillaux, Claude Thermes, Michelle Debatisse, Chun-Long Chen (2019 Dec 15)

Transcription-mediated organization of the replication initiation program across large genes sets common fragile sites genome-wide.

Nature communications : 5693 : DOI : 10.1038/s41467-019-13674-5