Decline of DNA damage response along with myogenic differentiation

Haser H Sutcu (1) , Phoebe Rassinoux (2) , Lise-Marie Donnio (2) , Damien Neuillet (2) , François Vianna-Legros (3) , Olivier Gabillot (1) , Pierre-Olivier Mari (2) , Céline Baldeyron (1) , Giuseppina Giglia-Mari (2)

1 IRSN/PSE-SANTE/SERAMED/LRAcc - Laboratoire de Radiobiologie des expositions accidentelles
2 PGNM - Pathophysiologie et génétique du neurone et du muscle
3 IRSN/PSE-SANTE/SDOS/LMDN - Laboratoire de micro-irradiation, de métrologie et de dosimétrie neutrons

DNA integrity is incessantly confronted to agents inducing DNA lesions. All organisms are equipped with a network of DNA damage response mechanisms that will repair DNA lesions and restore proper cellular activities. Despite DNA repair mechanisms have been revealed in replicating cells, still little is known about how DNA lesions are repaired in postmitotic cells. Muscle fibers are highly specialized postmitotic cells organized in syncytia and they are vulnerable to age-related degeneration and atrophy after radiotherapy treatment. We have studied the DNA repair capacity of muscle fiber nuclei and compared it with the one measured in proliferative myoblasts here. We focused on the DNA repair mechanisms that correct ionizing radiation (IR)-induced lesions, namely the base excision repair, the nonhomologous end joining, and the homologous recombination (HR). We found that in the most differentiated myogenic cells, myotubes, these DNA repair mechanisms present weakened kinetics of recruitment of DNA repair proteins to IR-damaged DNA. For base excision repair and HR, this decline can be linked to reduced steady-state levels of key proteins involved in these processes.

Domaines: Sciences du Vivant [q-bio]

Haser H Sutcu, Phoebe Rassinoux, Lise-Marie Donnio, Damien Neuillet, François Vianna-Legros, et al.. Decline of DNA damage response along with myogenic differentiation. Life Science Alliance, 2023, 7 (2), pp.e202302279. ⟨10.26508/lsa.202302279⟩. ⟨hal-04302036v2⟩