Area B: Modifications on Proteins

Crosstalk between PARylation, m6A methylation and cGAS activation upon induction of DNA

Recruitment of the ‘epigenetic’ RNA methyltransferase METTL3 to induced DNA damage sites requires activation of the PARP1/2 enzymes, but also requires active gene transcription and correlates with the accumulation of DNA–RNA hybrids. In a first project, we will dissect the underlying molecular mechanism(-s) and to establish the functional biological impact of this observation, notably in a DNA damage context. In parallel, we will explore how inhibition of PARP enzymes with small molecule inhibitors leads to the activation of cGAS and whether the relocalization of nuclear cGAS to the cytoplasm is impacted by PARP inhibitors.