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

Ana Teixeira-Silva, Anissia Ait Saada, Julien Hardy, Ismail Iraqui, Marina Charlotte Nocente, Karine Fréon, Sarah A E Lambert (2017 Dec 8)

The end-joining factor Ku acts in the end-resection of double strand break-free arrested replication forks.

Nature communications : 1982 : DOI : 10.1038/s41467-017-02144-5
Michelle Newman, Rym Sfaxi, Abhijit Saha, David Monchaud, Marie-Paule Teulade-Fichou, Stéphan Vagner (2017 Oct 27)

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

Journal of Molecular Biology : 429 : 3121-3131 : DOI : 10.1016/j.jmb.2016.11.033
Alexis Fouquin, Josée Guirouilh-Barbat, Bernard Lopez, Janet Hall, Mounira Amor-Guéret, Vincent Pennaneach (2017 Oct 3)

PARP2 controls double-strand break repair pathway choice by limiting 53BP1 accumulation at DNA damage sites and promoting end-resection.

Nucleic acids research : DOI : 10.1093/nar/gkx881
Elias Bou Samra, Géraldine Buhagiar-Labarchède, Christelle Machon, Jérôme Guitton, Rosine Onclercq-Delic, Michael R Green, Olivier Alibert, Claude Gazin, Xavier Veaute, Mounira Amor-Guéret (2017 Sep 27)

A role for Tau protein in maintaining ribosomal DNA stability and cytidine deaminase-deficient cell survival.

Nature communications : 693 : DOI : 10.1038/s41467-017-00633-1
Elie Hatem, Nadine El Banna, Meng-Er Huang (2017 May 24)

Multifaceted roles of glutathione and glutathione-based systems in carcinogenesis and anticancer drug resistance.

Antioxidants & redox signaling : DOI : 10.1089/ars.2017.7134
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