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List of research teams

Translesional polymerases, genomic plasticity, and cancer

Thematic(s)
Epigenetics, Genetics / Genomics, Innovative Therapies, Molecular and Cellular Biology
Attachment unit
UMR9019 - Genome Integrity and Cancer
Manager(s)
Patricia Kannouche
Institutional connection

Gustave Roussy, CNRS, Paris-Saclay University

Summary

Our team seeks to unravel the molecular mechanisms of mutagenesis and DNA damage tolerance, with a particular focus on translational lesion synthesis (TLS) DNA polymerases, which are involved in both tumor initiation and resistance to anticancer therapies. We combine approaches from cell and molecular biology, functional genomics, genome editing, and genomic and epigenomic profiling, using complementary models: normal and tumor cells, patient-derived organoids (PDOs), tumor–immune cell co-cultures, and mouse models.

Our basic research projects aim in particular to: (i) determine the role of polymerase ζ (Polζ) in the replication and stability of repetitive regions of the genome; (ii) understand the extreme susceptibility to UV-induced skin cancers in patients with Xeroderma Pigmentosum Variant (XP-V), who are deficient in η polymerase (POLH); and (iii) elucidating the mechanisms of mutagenesis in XPC-deficient cells by identifying the endogenous lesions involved and the contribution of different TLS polymerases to their tolerance.

More recently, we have expanded our research into translational oncology, in close collaboration with clinicians (B. Pistilli, Breast Cancer Committee) at Gustave Roussy. In particular, we seek to decipher the molecular mechanisms of sensitivity and resistance to antibody-drug conjugates (ADCs), which may involve pathways involved in the response to and tolerance of DNA damage. The goal is to identify tumor adaptation mechanisms, predictive biomarkers, and new therapeutic vulnerabilities using preclinical and clinically relevant models.

Team members

  • Patricia KANNOUCHE - Team Leader

    Director of Research and Equivalents, CNRS

     

    Said Aoufouchi

    Research Associate and Equivalents, INSERM

     

    Vianney Baris

    Research Engineer or equivalent, Gustave Roussy

     

    DE OLIVEIRA Luciana Marcia

    Research Engineer or equivalent, Gustave Roussy

     

    Virgile Gibert

    Ph.D. student, Paris-Saclay University

     

    Basile Guignier

    Postdoctoral researcher, Gustave Roussy

     

    Anne HELBLING-LECLERC

    Assistant Professor, Paris-Saclay University

     

    KLEIN, Alexis

    Ph.D. Candidate, Paris-Saclay University

     

    Frédérique Maczkowiak

    Research Engineer or equivalent, CNRS

     

    Benedetta Mancini

    Ph.D. student, Gustave Roussy

     

    Li MEIKUN

    Ph.D. student, Paris-Saclay University

     

    Jean Paul MOUSSU

    Engineering Assistant or equivalent, CNRS

     

    Carla NOORMAMADE DA-CUNHA

    Research Technician or equivalent, Gustave Roussy

     

    ODIC Baptiste

    Design Engineer or equivalent, Gustave Roussy

     

    PEREIRA Emma

    Ph.D. Student, Paris-Saclay University

     

    Caroline POUVELLE 

    Research Technician or equivalent, CNRS

     

    ROSSELLI Filippo

    Research Director or equivalent, CNRS

     

    Esra-Nour SENTURK

    Engineering Assistant or equivalent, CNRS

Key publications

  • TASP1-mediated cleavage of REV3L enhances the activity of DNA polymerase ζ in mammalian cells. Nat Commun. 2026 Jun 15.

    Goulas J*, Guignier B*, Ben Yamin B*, Pouvelle C, Yurchenko A, Despras E, de Oliveira L, Laplante P, Bochaton D, Plassard D, Yang W, Theillet FX, Veaute X, Wood RD, Nikolaev S, Cordonnier AM, Kannouche PL. 

  • Changes in the architecture and abundance of replication intermediates delineate the chronology of DNA damage tolerance pathways at UV-stalled replication forks in human cells. Nucleic Acids Res. 2022 Sep 23;50(17):9909-9929.

    Benureau Y, Pouvelle C, Dupaigne P, Baconnais S, Moreira Tavares E, Mazón G, Despras E, Le Cam E, Kannouche PL. 

  • Expression of a Constitutive Fusion of Ubiquitin to PCNA Restores the Level of Immunoglobulin A/T Mutations During Somatic Hypermutation in the Ramos Cell Line. Front Immunol. 2022 Apr 1;13:871766

    Lerner LK, Bonte D, Le Guillou M, Mohammad MM, Kasraian Z, Sarasin A, Despras E, Aoufouchi S. 

  • DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability. EMBO J. 2021 Nov 2;40(21):e104543.

    Ben Yamin B, Ahmed-Seghir S, Tomida J, Despras E, Pouvelle C, Yurchenko A, Goulas J, Corre R, Delacour Q, Droin N, Dessen P, Goidin D, Lange SS, Bhetawal S, Mitjavila-Garcia MT, Baldacci G, Nikolaev S, Cadoret JC, Wood RD, Kannouche PL. 

  • Patritumab deruxtecan in HR+HER2- advanced breast cancer: a phase 2 trial. Nat Med. 2025 Oct;31(10):3492-3503

    Pistilli B, Mosele F, Corcos N, Pierotti L, Pradat Y, Le Bescond L, Lacroix-Triki M, Nachabeh G, Alfaro A, Catelain C, Job B, Mami-Chouaib F, Badel S, Farace F, Oulhen M, Kannouche P, Tran DTN, Droin N, Vicier C, Frenel JS, D'Hondt V, Dalenc F, Bachelot T, Ducoulombier A, Benderra MA, Loirat D, Mayeur D, Deluche E, Deneuve J, Cheikh-Hussin R, Guyader P, Signolle N, Godefroy K, Talbot H, Vakalopoulou M, Christodoulidis S, Bernard E, Koudou Y, Sporchia A, Suto F, Li L, Sternberg DW, Michiels S, André F, Sellami D, Montagnac G. 

Contacts

Location: Gustave Roussy Institute