DNA damage recognition and repair

Our team has a long-standing interest in the DNA repair machinery of D. radiodurans, which is known to contribute to the survival of D. radiodurans after exposure to high doses of UV or ionizing radiation (Timmins and Moe, 2016).

We are particularly interested in the early steps of DNA repair during which the repair machinery detects and eliminates DNA lesions within a vast excess of undamaged DNA. This process is comparable to looking for a needle in a haystack !

Our research focuses on the base excision (BER) and nucleotide excision (NER) repair pathways, which together are responsible for eliminating all damages occurring at the nucleotide level. We perform structural and functional studies of the major proteins involved in these pathways, and because DNA damage recognition relies on transient protein-DNA and protein-protein interactions, we also explore the dynamics of these processes.

Collaborations

• Jean-Luc RAVANAT (CEA/SyMMES, Grenoble)
• François DEHEZ (LPCT, Nancy)
• Elin MOE (ITQB, Lisbon, Portugal)

Recent publications

Moe E, Silveira CM, Zuccarello L, Rollo F, Stelter M, De Bonis S, Kulka-Peschke C, Katz S, Hildebrandt P, Zebger I, Timmins J & Todorovic S. Human Endonuclease III/NTH1 : Focusing on the [4Fe-4S] cluster and the N-terminal domain. Chem Comm (2022). DOI : 10.1039/D2CC03643F.
Seck A, De Bonis S, Saint-Pierre C, Gasparutto D, Ravanat JL & Timmins J. In vitro reconstitution of an efficient nucleotide excision repair system using mesophilic enzymes from Deinococcus radiodurans. Communications Biology (2022). 5, 127. DOI : 10.1038/s42003-022-03064-x.
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.
Timmins J and Moe E. A decade of biochemical and structural studies of the DNA repair machinery of Deinococcus radiodurans. Review article. Comput Struct Biotechnol J. (2016) 14 p. 168-176. DOI : 10.1016/j.csbj.2016.04.001.
Sarre A, Ökvist M, Klar T, Hall DR, Smålas A, McSweeney S, Moe E and Timmins J. Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans. Journal of Structural Biology (2015) 191 (2) p. 87-99. DOI : 10.1016/j.jsb.2015.05.009.