Thierry Douki & Jean-Luc Ravanat

Sunlight exhibits numerous positive effects on human health such as the synthesis of vitamin D. However, overexposure is associated with a large number of deleterious processes. The UV portion of the emission spectrum of sunlight is the most damaging. The main targeted organs are those directly exposed to sun rays namely skin and the eyes. Systemic effects such as immunosuppression are also observed. In skin, the most drastic effects are photoaging and induction of skin cancer. The latter process is largely explained by the fact that UV leads to DNA damage. Upon cell division, this damage induce mutations that can activate proto-oncogenes or inactivate tumor suppressor genes. DNA damage also play a role of sensor in the cellular response to UV exposure, for example in the induction of erythema or pigmentation. A first action of CIBEST on this topic is the understanding of parameters that affect the nature and the amount of DNA damage produced by UV radiation. This work is done from a very basic level in test tube experiments involving isolated DNA models to in vitro studies using cells, primary cultures of skin cells, whole skin explants and 3D models such as reconstituted skin. A large amount of work has been devoted to the study of the respective effects of UVB, the most energetic photons in sunlight and the less frequent (less than 5%) and UVA (less energetic but much more frequent. Quantification of DNA damage is also used as biomarker in the evaluation of photoprotection products.

In order to counteract the consequences of UV-induced damage, cells rely on several processes. The first step is an arrest of the division that, in particular, allows cells to handle damage to their genome. If the extent of damage is too severe, cells trigger a programmed cell death called apoptosis. When the level of damage is low enough, DNA is repaired with elimination of the damaged sites and restauration of the correction sequences. CIBEST is actively involved in the study of this important response of skin to UV exposure. Several studies, mostly performed in collaboration with other groups, aimed at identifying cellular parameters such as the role of the AhR factor or of cellular energetics in DNA repair. CIBEST also perform studies related to DNA repair diseases. Several syndromes have been identified in which patients are born with mutations in the DNA repair genes. These conditions are associated with decreased repair capacities and increased rate of skin cancer. The work done at CIBEST aims at quantifying the extent of repair deficiency as well has the associated mechanisms.

Photobiology is not only relevant to human health but also concerns numerous living organisms. CIBEST has been involved in many research works on microorganisms. First, we collaborate with several groups on the formation of UV-induced DNA damage in bacterial spores. Because of very specific cellular environment, the photochemistry and the DNA repair mechanisms are drastically different from other cell types. We worked on marine bacteria and algae with the purpose of quantifying DNA damage under specific exposure conditions and to study DNA repair systems, which are not present in humans: the photolyases. These enzymes have the particularity of reversing the DNA damage by using photochemical processes trigger by sunlight.