Control of alternative end joining by the chromatin remodeler p400 ATPase.

Repair of DNA double-strand breaks occurs in a chromatin context that needs to be modified and remodeled to allow suitable access to the different DNA repair machineries. Of particular importance for the maintenance of genetic stability is the tight control of error-prone pathways, such as the alternative End Joining pathway. Here, we show that the chromatin remodeler p400 ATPase is a brake to the use of alternative End Joining.

H2A.Z depletion impairs proliferation and viability but not DNA double-strand breaks repair in human immortalized and tumoral cell lines.

In mammalian cells, DNA double-strand breaks (DSB) can be repaired by 2 main pathways, homologous recombination (HR) and non-homologous end joining (NHEJ). To give access to DNA damage to the repair machinery the chromatin structure needs to be relaxed, and chromatin modifications play major roles in the control of these processes. Among the chromatin modifications, changes in nucleosome composition can influence DNA damage response as observed with the H2A.

Myostatin induces atrophy of trout myotubes through inhibiting the TORC1 signaling and promoting Ubiquitin-Proteasome and Autophagy-Lysosome degradative pathways.

Myostatin (MSTN) is well known as a potent inhibitor of muscle growth in mammals and has been shown to both inhibit the growth promoting TORC1 signaling pathway and promote Ubiquitin-Proteasomal and Autophagy-Lysosomal degradative routes. In contrast, in non-mammalian species, despite high structural conservation of MSTN sequence, functional conservation is only assumed. Here, we show that treatment of cultured trout myotubes with human recombinant MSTN (huMSTN) resulted in a significant decrease of their diameter by up to 20%, validating the use of heterologous huMSTN in our in vitro model to monitor the processes by which this growth factor promotes muscle wasting in fish.