Ribosomal stress, ribosomal DNA stability and cellular senescence: role of PML
Ribosome biogenesis is highly coordinated and energy demanding process consuming more than 60% of cellular energy sources. The disturbance of assembly of ribosomes and protein translation disorders cellular homeostasis and may cause ribosomopathies and cancer. rDNA repeats represent a most unstable component of eukaryotic genome. Mechanisms controlling the stability of rDNA regions in mammals cells are not understood. There is emerging evidence that rDNA instability is related to cellular lifespan and development of aging disorders and aging in general. The main goal of this project is to unravel mechanisms of the rDNA stability during ribosomal stress and cellular senescence and the role of PML in these processes. The specific aims include investigation of changes of rDNA copy number during ribosomal stress and cellular senescence, role of homologous recombination in maintenance of rDNA stability and understanding synergy between inactivation of RNA polymerase I and topological stress.