
Genome expression and repair
Members
Researchers
Post-doctoral fellows
PhD students
Engineers
Trainees
Former members
- Dr Laurent Schaeffer, Director of Institut NeuroMyoGene
- Dr. Valentyn Oksenych, PI NTNU
- Dr. Pierre Chymkovitch, PI Oslo University Hospital
Genome expression and repair
Transcription, one of the key steps in gene expression in response to various stimuli in the body, such as stress or hormones, requires a combination of factors. The harmful action of chemical or physical agents that cause damage to DNA disrupts gene expression. If these lesions are not removed by effective repair systems, they will cause mutations that can lead to cancer or increase aging. TFIIH, a complex made up of ten subunits, plays a key role in both gene transcription and gene repair. Mutations in some of the TFIIH subunits are responsible for three genetic diseases, xeroderma pigmentosum (XP), trichotyodystrophy (TTD) and Cockayne syndrome (CS), the phenotype of which results from defects in both DNA repair and gene expression. XP patients develop melanoma very early in life, while TTD and CS patients age prematurely. With the help of biochemistry, genetics and cell biology, we are studying the mechanisms of aging and cancer in various cell systems and animal models deficient in DNA repair and transcription. We are also developing a research axis on melanoma aimed in particular at establishing new therapeutic solutions against this cancer.
Current projects
Our objective is to improve our understanding of the mechanisms that regulate the expression of genes encoding proteins at the transcriptional level and their maintenance of their integrity. The growing amount of data shows that the expression and maintenance of the integrity of genetic information are intimately linked. Errors in each of these crucial cellular mechanisms lead to somatic or hereditary diseases like cancer, but are also involved in natural mechanisms like aging. Our team tries to answer the following questions :
- How do repair and transcription factors participate in the transactivation of specific genes? • How is transcription related to DNA repair?
- How do mutations found in genetic diseases affect the transcriptional program of a specific cell that causes somatic diseases such as cancer or hormonal dysfunction?
- How does the effectiveness of removing DNA damage play a role in cancer treatment or aging?
- Can we target DNA expression or repair to kill cancer cells?
- What are the transcriptional deregulations that predominate in cancer cells?
Collaborations and networks
- Dr. Poterszman, IGBMC: Structure/function of TFIIH
- Dr. Davidson, IGBMC: TFIIH and melanoma
- Dr. Ali Hamiche, IGBMC: Chromatine remodeling and histone variants
- Pr J. Kraemer, National Cancer Institute, Bethesda, USA: XP, CS and TTD patients
- Pr. M. Zurita, Universidad Nacional Autónoma de México, Cuernavaca, Mexico: Drosophila models of XP, CS and TTD
- Dr. J. Svestrup, Clare Hall Laboratories, Cancer Research UK London Research Institute, UK: Gene expression
- Dr. P. Brousset, Université Paul-Sabatier, Toulouse, France: Biology of cancer
Funding and partners
ANR
Fondation ARC
INCA
Labélisation Ligue contre le Cancer
PharmaMar company
Awards and recognitions
- Prix scientifique - Comité Alsace de la Fondation pour la Recherche Médicale (FRM) - 2014
- Prix Olga Sain - La ligue contre le cancer - 2013
- Grand Prix - Fondation pour la recherche médicale (FRM) - 2012
- Prix Henry et Mary-Jane Mitjaville - Académie Nationale de Médecine - 2009
- Prix Duquesne - Ligue Nationale contre le Cancer de Paris - 2009
- Prix Charles-Louis de Saulses de Freycinet - Institut de France de l'Académie des Sciences - 2008
- ERC Advanced grant - European Research Council (ERC) - 2008
- Membre de l'Académie des sciences - Académie des sciences - 2006
- Chevalier de la Légion d’Honneur - Etat français - 2006
- Grand Prix - Inserm - 2004
- Prix AGF/Athena - Institut de France de l'Académie des Sciences - 2002
- Prix Descartes - European Economic Community - 2000
- Membre de l'organisation européenne de biologie moléculaire (EMBO) - European Molecular Biology Organization (EMBO) - 1998
- Prix Européen Jeanne Loubaresse - Institut Curie - 1997
- Chevalier de l'Ordre National du Mérite - Etat français - 1996
- Prix Tartois - Fondation pour la Recherche Médicale (FRM) - 1996
Publications
2016
Lurbinectedin Specifically Triggers the Degradation of Phosphorylated RNA Polymerase II and the Formation of DNA Breaks in Cancer Cells
- Gema Santamaría Nuñez
- Carlos Mario Genes Robles
- Christophe Giraudon
- Juan Fernando Martínez-Leal
- Emmanuel Compe
- Frédéric Coin
- Pablo Aviles
- Carlos María Galmarini
- Jean-Marc Egly
Molecular Cancer Therapeutics ; Volume: 15 ; Page: 2399-2412
2015
Revisiting the Function of CDK7 in Transcription by Virtue of a Recently Described TFIIH Kinase Inhibitor
- Frédéric Coin
- Jean-Marc Egly
Molecular Cell ; Volume: 59 ; Page: 513-514
Orchestral maneuvers at the damaged sites in nucleotide excision repair
- Sergey Alekseev
- Frédéric Coin
Cellular and Molecular Life Sciences ; Volume: 72 ; Page: 2177-2186
TFIIH Subunit Alterations Causing Xeroderma Pigmentosum and Trichothiodystrophy Specifically Disturb Several Steps during Transcription
- Frédéric Coin
- Amita Singh
- Emanuel Compe
- Nicolas Le may
- Jean-Marc Egly
American Journal of Human Genetics ; Volume: 96 ; Page: 194-207
2014
ZFC3H1, a Zinc Finger Protein, Modulates IL-8 Transcription by Binding with Celastramycin A, a Potential Immune Suppressor
- Takeshi Tomita
- Katsuaki Ieguchi
- Frédéric Coin
- Yasuhiro Kato
- Haruhisa Kikuchi
- Yoshiteru Oshima
- Shoichiro Kurata
- Yoshiro Maru
PLoS ONE ; Volume: 9 ; Page: e108957
Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin
- Salim Ziani
- Zita Nagy
- Sergey Alekseev
- Evi Soutoglou
- Jean-Marc Egly
- Frédéric Coin
Journal of Cell Biology ; Volume: 206 ; Page: 589-598
A Small Molecule Screen Identifies an Inhibitor of DNA Repair Inducing the Degradation of TFIIH and the Chemosensitization of Tumor Cells to Platinum
- Sergey Alekseev
- Mériam Ayadi
- Laurent Brino
- Jean-Marc Egly
- Annette k. Larsen
- Frédéric Coin
Chemistry and Biology ; Volume: 21 ; Page: 398-407
2013
ELL, a novel TFIIH partner, is involved in transcription restart after DNA repair
- S. Mourgues
- V. Gautier
- A. Lagarou
- C. Bordier
- A. Mourcet
- J. Slingerland
- L. Kaddoum
- Frédéric Coin
- W. Vermeulen
- A. Gonzales de Peredo
- B. Monsarrat
- P.-O. Mari
- G. Giglia-Mari
Proceedings of the National Academy of Sciences of the United States of America ; Volume: 110 ; Page: 17927-17932
Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack
- Valentyn Oksenych
- Alexander Zhovmer
- Salim Ziani
- Pierre-Olivier Mari
- Jitka Eberova
- Tiziana Nardo
- Miria Stefanini
- Giuseppina Giglia-Mari
- Jean-Marc Egly
- Frédéric Coin
PLoS Genetics ; Volume: 9 ; Page: e1003611
Regulatory interplay of Cockayne syndrome B ATPase and stress-response gene ATF3 following genotoxic stress
- U. Kristensen
- A. Epanchintsev
- M.-A. Rauschendorf
- V. Laugel
- T. Stevnsner
- V. Bohr
- Frédéric Coin
- J.-M. Egly
Proceedings of the National Academy of Sciences of the United States of America ; Volume: 110 ; Page: E2261-E2270