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

Anissia Ait Saada, Ana Teixeira-Silva, Ismail Iraqui, Audrey Costes, Julien Hardy, Giulia Paoletti, Karine Fréon, Sarah A E Lambert (2017 May 4)

Unprotected Replication Forks Are Converted into Mitotic Sister Chromatid Bridges.

Molecular cell : 398-410.e4 : DOI : 10.1016/j.molcel.2017.04.002
Simon Gemble, Géraldine Buhagiar-Labarchède, Rosine Onclercq-Delic, Christian Jaulin, Mounira Amor-Guéret (2017 May 2)

Cytidine deaminase deficiency impairs sister chromatid disjunction by decreasing PARP-1 activity.

Cell cycle (Georgetown, Tex.) : 1-8 : DOI : 10.1080/15384101.2017.1317413
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 (2017 Apr 15)

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
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 7)

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