Institut de Biologie StructuraleGrenoble / France

Contact person(s) related to this article / TIMMINS Joanna

Genome Organisation & Maintenance (GenOM) Team

Team leader: Joanna Timmins

Presentation

The prime objective of every life form is to deliver its genetic material, intact and unchanged, to the next generation, despite constant assaults from both endogenous and exogenous sources, such as UV light, ionizing radiation or genotoxic anticancer agents. DNA damage blocks genome replication and transcription, and if left unrepaired, DNA lesions can lead to mutations or wider-scale genome aberrations that threaten cell or organism viability. To counter this threat, cells have evolved several elaborate DNA damage response systems.

Our team aims to better understand the fundamental mechanisms involved in the coordinated response of cells to DNA damage and to determine how such processes can contribute to radiation resistance in bacteria and to drug resistance in cancer cells.

To achieve these objectives, we use a highly integrated approach combining molecular biology, biochemistry, structural biology and advanced live cell imaging.

Our favourite model organism is one of the most radiation resistant organisms on earth, the bacterium Deinococcus radiodurans. We also use eukaryotic models for our work on cancer-related topics.


Research projects

Our current research projects fall into three areas:

1 - Structure and dynamics of the nucleoid .
2 - DNA damage recognition and repair.
3 - DNA repair in anti-cancer drug resistance.

Funding

Keywords

Deinococcus radiodurans; Nucleoid organisation and dynamics; DNA repair; DNA damage recognition; Radiation resistance; Cancer; Anticancer drug resistance.

Current members

• Anne-Sophie BANNEVILLE, PhD CEA
• Salvatore DE BONIS, Tech CEA
• Fabienne HANS, MCF-HC UGA
• Jean-Philippe KLEMAN, E6 CEA
• Françoise LACROIX, IEHC CNRS
• Joanna TIMMINS, DR2 CNRS
• Pierre VAUCLARE, CRCN CNRS

Past members

• Anna Seck (PhD; 2017-2021)
• Kevin Floc’h (PhD; 2015-2019) Thesis
• Müge Senarisoy (PhD; 2015-2018) Thesis
• Anthi Mettou (Post-doc; 2017-2019)
• Meike Stelter (Post-doc; 2011-2015)
• Aili Sarre (PhD; 2012-2014)

Techniques:

• Molecular biology
• Microbiology
• Mammalian cell culture
• Expression and purification of proteins
• Biochemical & biophysical characterisation
• Macromolecular crystallography
• Conventional and super-resolution fluorescence microscopy
• Flow cytometry

Latest publications

Jessop M, Liesche C, Felix J, Desfosses A, Baulard M, Adam V, Fraudeau A, Huard K, Effantin G, Kleman JP, Bacia-Verloop M, Bourgeois D and Gutsche, I. Supramolecular assembly of the E. coli LdcI upon acid stress. Proc. Nat. Acad. Sci. (2021). 118 (2), e2014383118. DOI: 10.1073/pnas.2014383118.

Hans F, Senarisoy M, Bhaskar Naidu C and Timmins J. Focus on DNA glycosylases – A set of tightly regulated enzymes with high potential as anticancer drug targets. (Review) Int. J. Mol. Sci., Special issue: Recognition of DNA lesions. (2020). 21 (23), 9226. DOI: 10.3390/ijms21239226.

Chen SW, Banneville A-S, Teulon J-M, Timmins J and Pellequer J-L. Nanoscale surface structures of DNA bound to Deinococcus radiodurans HU unveiled by atomic force microscopy. Nanoscale (2020) 12, 22628. DOI: 10.1039/D0NR05320A.

Fouët G, Gout E, Wicker-Planquart C, Bally I, De Nardis C, Dedieu S, Chouquet A, Gaboriaud C, Thielens NM, Kleman JP and Rossi V. Complement C1q interacts with LRP1 Clusters II and IV through a site close but different from the binding site of Its C1r and C1s-Associated proteases. Front. Immunol. (2020) 11, 583754. DOI: 10.3389/fimmu.2020.583754.

Guseva S, Milles S, Jensen MR, Salvi N, Kleman JP, Maurin D, Ruigrok RWH and Blackledge M. Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly. Sci. Adv. (2020), 6 (14), eaaz7095. DOI: 10.1126/sciadv.aaz7095.

Vauclare P, Natali F, Kleman JP, Zaccai G and Franzetti, B. Surviving salt fluctuations: stress and recovery in Halobacterium salinarum, an extreme halophilic Archaeon. Scientific Reports (2020), 10 (1), 3298. DOI: 10.1038/s41598-020-59681-1.

Senarisoy M, Barette C, Lacroix F, De Bonis S, Stelter M, Hans F, Kleman JP, Fauvarque M-O and Timmins J. Förster resonance energy transfer-based biosensor for targeting the hNTH1-YB1 interface as a potential anti-cancer drug target. ACS Chemical Biology (2020) 15, 4, 990-1003. DOI: 10.1021/ acschembio.9b01023.

Mandula O, Kleman JP, Lacroix F, Allier C, Fiole D, Hervé L, Blandin P, Kraemer DC, Morales S. Phase and fluorescence imaging with a surprisingly simple microscope based on chromatic aberration. Opt. Express. (2020) 28 (2), 2079-2090. DOI: 10.1364/OE.28.002079.

Hognon C, Garaude S, Timmins J, Chipot C, Dehez F and Monari A. Molecular basis of DNA packaging in bacteria revealed by all-atoms molecular dynamic simulations: The case of histone-like proteins in Borrelia burgdorferi. J. Phys. Chem. Lett. (2019) 10, 7200-7207. DOI: 10.1021/acs.jpclett.9b02978.

Floc’h K, Lacroix F, Servant P, Wong YS, Kleman JP, Bourgeois D and Timmins J. Cell morphology and nucleoid dynamics in dividing D. radiodurans. Nat Commun. (2019) 10 (1). p.3815. DOI: 10.1038/s41467-019-11725-5.

Sarre A, Stelter M, Rollo F, De Bonis S, Seck A, Hognon C, Ravanat JL, Monari A, Dehez F, Moe E and Timmins J. The three Endonuclease III variants of Deinococcus radiodurans possess distinct and complementary DNA repair activities. DNA Repair (2019) 78 p. 45-59. DOI: 10.1016/j.dnarep.2019.03.014.

Wiegand T, Cadalbert R, Lacabanne D, Timmins J, Terradot L, Böckmann A, Meier BH. The conformational events coupling ATP hydrolysis and translocation in a bacterial DnaB helicase. Nat Commun. (2019) 10 (1). p.31. DOI: 10.1038/s41467-018-07968-3.

Floc’h K, Lacroix F, Barbieri L, Servant P, Galland R, Butler C, Sibarita JB, Bourgeois D and Timmins J. Bacterial cell wall nanoimaging by autoblinking microscopy. Scientific Reports (2018) 8 (1) p. 14038. DOI: 10.1038/s41598-018-32335-z.