UMR3348 – Genotoxic stress and Cancer

The prevention of genomic instability and cancer depends on the optimal functions of a complex network of pathways collectively called the DNA damage response (DDR).

The research activities of our unit span several aspects of the DDR, intracellular signalling and genome stability in response to genotoxic stress, either from endogenous sources (e.g. replication stress, mutations in oncogenes and tumor suppressor genes) or from exogenous sources (e.g. oxidative stress, chemotherapeutic agents, ionizing and UV radiation).

We are particularly interested by the functional relationships between what we call the “6Rs”: Replication, Repair, Recombination, RNA biology, Redox regulation and responses to Radiations.

We specifically want to focus on:

  • The network of cellular responses to exogenous and endogenous stresses,
  • The influence of cell stress responses on cancer susceptibility and treatment efficacy,
  • The hijacking of stress-induced responses for the development of new anti-cancer therapies.

The wide range of expertise of our teams in molecular and cellular biology, genetics and biochemistry allows us to address these issues by using a great variety of technological approaches and several model systems  (yeast, mammalian cell lines, animal models).

Key publications

Year of publication 2017

Hermela Shimelis, Romy L S Mesman, Catharina Von Nicolai, Asa Ehlen, Lucia Guidugli, Charlotte Martin, Fabienne Mgr Calleja, Huong Meeks, Emily Hallberg, Jamie Hinton, Jenna Lilyquist, Chunling Hu, Cora M Aalfs, Kristiina Aittomaki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Matthias W Beckmann, Javier J Benitez, Natalia Bogdanova, Stig E Bojesen, Manjeet K Bolla, Anne-Lise Borresen-Dale, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Annegien Broeks, Barbara Brouwers, Thomas Bruning, Barbara Burwinkel, Jenny Chang-Claude, Georgia Chenevix-Trench, Ching-Yu Cheng, Ji-Yeob Choi, J Margriet Collée, Angela Cox, Simon S Cross, Kamila Czene, Hatef Darabi, Joe Dennis, Thilo Dork, Isabel Dos Santos Silva, Alison M Dunning, Peter A Fasching, Jonine D Figueroa, Henrik Flyger, Montserrat Garcia-Closas, Graham G Giles, Gord Glendon, Pascal Guenel, Christopher A Haiman, Per Hall, Ute Hamann, Mikael Hartman, Frans B L Hogervorst, Antoinette Hollestelle, John L Hopper, Hidemi Ito, Anna Jakubowska, Daehee Kang, Veli-Matti Kosma, Vessela Kristensen, Kah-Nyin Lai, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Annika Lindblom, Artitaya Lophatananon, Jan Lubinski, Eva Machackova, Arto Mannermaa, Sara Margolin, Frederik Marme, Keitaro Matsuo, Hui Miao, Kyriaki Michailidou, Roger L Milne, Kenneth Muir, Susan L Neuhausen, Heli Nevanlinna, Janet E Olson, Curtis Olswold, Jan C Oosterwijk, Ana Osorio, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Katri Pylkäs, Paolo Radice, Muhammad U Rashid, Valerie Rhenius, Anja Rudolph, Suleeporn Sangrajrang, Elinor J Sawyer, Marjanka K Schmidt, Minouk J Schoemaker, Caroline M Seynaeve, Mitul Shah, Chen-Yang Shen, Martha J Shrubsole, Xiao-Ou Shu, Susan L Slager, Melissa C Southey, Daniel O Stram, Anthony J Swerdlow, Soo Hwang Teo, Ian Tomlinson, Diana Torres, Therese Truong, Christi J van Asperen, Lizet E van der Kolk, Qin Wang, Robert Winqvist, Anna H Wu, Jyh-Cherng Yu, Wei Zheng, Ying Zheng, Jennifer Leary, Logan C Walker, Lenka Foretova, Florentia Fostira, Kathleen Claes, Liliana Varesco, Setareh Moghadasi, Douglas F Easton, Amanda B Spurdle, Peter Devilee, Harry Vrieling, Alvaro N Monteiro, David E Goldgar, Aura Carreira, Maaike P G Vreeswijk, Fergus J Couch (2017 Mar 10)

BRCA2 hypomorphic missense variants confer moderate risks of breast cancer.

Cancer research : DOI : 10.1158/0008-5472.CAN-16-2568
Rocchetti F, Tran Quang C, Maragno AL, Nguyen J, Lasgi C, Ghysdael J. (2017 Jan 1)

The calcineurin protein phosphatase is dispensable for BCR-ABL-induced B-ALL maintenance, propagation and response to dasatinib.

Leukemia : DOI : 10.1038/leu.2016.269

Year of publication 2016

Michelle Newman, Rym Sfaxi, Abhijit Saha, David Monchaud, Marie-Paule Teulade-Fichou, Stéphan Vagner (2016 Dec 13)

The G-Quadruplex-Specific RNA Helicase DHX36 Regulates p53 Pre-mRNA 3′-End Processing Following UV-Induced DNA Damage.

Journal of molecular biology : S0022-2836(16)30528-9 : DOI : 10.1016/j.jmb.2016.11.033
Catharina von Nicolai, Åsa Ehlén, Charlotte Martin, Xiaodong Zhang, Aura Carreira (2016 Sep 15)

A second DNA binding site in human BRCA2 promotes homologous recombination.

Nature communications : 12813 : DOI : 10.1038/ncomms12813
Amélie Trinquand, Nuno R Dos Santos, Christine Tran Quang, Francesca Rocchetti, Benedetta Zaniboni, Mohamed Belhocine, Cindy Da Costa de Jesus, Ludovic Lhermitte, Melania Tesio, Michael Dussiot, François-Loïc Cosset, Els Verhoeyen, Françoise Pflumio, Norbert Ifrah, Hervé Dombret, Salvatore Spicuglia, Lucienne Chatenoud, David-Alexandre Gross, Olivier Hermine, Elizabeth Macintyre, Jacques Ghysdael, Vahid Asnafi (2016 Sep 6)

Triggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia.

Cancer discovery : 972-85 : DOI : 10.1158/2159-8290.CD-15-0675
Hamza Mameri, Ivan Bieche, Dider Meseure, Elisabetta Marangoni, Géraldine Buhagiar-Labarchède, Andre Nicolas, Sophie Vacher, Rosine Onclercq-Delic, Vinodh Rajapakse, Sudhir Varma, William C Reinhold, Yves Pommier, Mounira Amor-Guéret (2016 Sep 6)

Cytidine deaminase deficiency reveals new therapeutic opportunities against cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research : DOI : 10.1158/1078-0432.CCR-16-0626