The promyelocytic leukemia protein and nuclear domain function in DNA damage signaling and repair.

The repository of genetic information in each of our cells is the nucleus. In eukaryotic cells, the nucleus is a highly organised and dynamic structure, complete with specialised compartments responsible for processes such as transcription, RNA splicing, DNA repair and replication. The various sub-nuclear compartments appear to serve as excellent markers for cellular health, often being disrupted in disease states such as cancer or viral infection. This concept is most elegantly demonstrated by the promyelocytic leukemia nuclear body (PML NB), which is disrupted in the white blood cells of patients with acute promyelocytic leukemia. PML NBs have also been implicated in DNA repair and tumour suppression. We have recently discovered that PML NBs respond to DNA damage by increasing in number through fission from pre-exisiting bodies. This response is regulated by cell cycle progression and several key molecular pathways that help to prevent cancer following DNA damage. PML NB numbers appears to provide a novel biomarker for the cellular response to DNA damage and control of cellular proliferation. Further characterization of the role of PML NBs in DNA repair will provide needed insight into how our cells respond to genotoxic stress and how this response is subverted during cancer development.