Rescue of replication failure by Fanconi anaemia proteins

Chromosomal aberrations are often associated with incomplete genome duplication, for instance at common fragile sites, or as a consequence of chemical alterations in the DNA template that block replication forks. Studies of the cancer-prone disease Fanconi anaemia (FA) have provided important insights into the resolution of replication problems. The repair of interstrand DNA crosslinks induced by chemotherapy drugs is coupled with DNA replication and controlled by FA proteins. We discuss here the recent discovery of new FA-associated proteins and the development of new tractable repair systems that have dramatically improved our understanding of crosslink repair. We focus also on how FA proteins protect against replication failure in the context of fragile sites and on the identification of reactive metabolites that account for the development of Fanconi anaemia symptoms

Out-of-equilibrium lattice response to photo-induced charge-transfer in a MnFe Prussian blue analogue

International audiencePhoto-induced structural dynamics in molecular materials often involve two main components; local molecular distortions induced by the self-trapping of electronic excited state and incoherent lattice dynamics due to energy dissipation. The latter component frequently hinders clear manifestation at macroscopic scale of local self-trapped entities and their coupling to the lattice. The studied photoactive MnFe Prussian blue analogue exhibits no thermal expansion, which allows observing long-range lattice dynamics induced by the structural trapping of photo-induced charge-transfer (CT) states. The self-trapping of the photo-induced (MnFeII)-Fe-III -> (MnFeIII)-Fe-II is responsible for the emergence of various physical properties. At equilibrium, the lattice volume expansion and the ferroelastic Jahn-Teller distortion associated with the charge-transfer-based phase transition, evolve in a coupled way. Here, we use time resolved X-ray diffraction to investigate the anisotropic out-of-equilibrium lattice dynamics triggered by the self-trapping of photo-induced (MnFeII)-Fe-III -> (MnFeIII)-Fe-II CT. The observed dynamics evidence a decoupling of both types of lattice deformations in the time domain, with an impulsive lattice response driven by the local Jahn-Teller reorganization and a displacive volume expansion controlled by the long-lived photo-induced CT small-polarons, due to the population of antibonding orbitals centered on Mn-N bonds in the (a,b) lattice plane