PML nuclear bodies: dynamic sensors of DNA damage and cellular stress.
Promyelocytic leukaemia nuclear bodies (PML NBs) are generally present in all mammalian cells, and their integrity correlates with normal differentiation of promyelocytes. Mice that lack PML NBs have impaired immune function, exhibit chromosome instability and are sensitive to carcinogens. Although their direct role in nuclear activity is unclear, PML NBs are implicated in the regulation of transcription, apoptosis, tumour suppression and the anti-viral response. An emerging view is that they represent sites where multi-subunit complexes form and where post-translational modification of regulatory factors, such as p53, occurs in response to cellular stress. Following DNA damage, several repair factors transit through PML NBs in a temporally regulated manner implicating these bodies in DNA repair. We propose that PML NBs are dynamic sensors of cellular stress, which rapidly disassemble following DNA damage into large supramolecular complexes, dispersing associated repair factors to sites of damage. The dramatically increased total surface area available would enhance interactions between PML-associated factors regulating DNA repair and apoptosis.
Dellaire
Graham
G
Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Bazett-Jones
David P
DP
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000502:physiology*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008954:Models, Biological; D011499:Protein Processing, Post-Translational