Chromatin Alterations in a Model of Oncogene Activation Studied by Advanced Fluorescence Microscopy

Defects in the global organization of chromatin are relevant in many pathological processes, including cancer. The activation of oncogenes has been recognized as a triggering event of alterations in the dynamics of replication, transcription and DNA damage response (DDR), that may lead to increased DNA damage and the onset of genomic instability [Negrini et al, Nature Rev Mol Cell Biol (2010)]. Genome-wide sequencing methods are shedding light on the series of molecular events (e.g. replication stress) that follow oncogene activation and produce genomic damage [Macheret and Halazonetis, Nature (2018)]. However, how these events are unfolding in the context of the crowded three-dimensional nucleus and which is the role of nanoscale chromatin architecture remain to be determined yet.