Proteasome-dependent dispersal of PML nuclear bodies in response to alkylating DNA damage.
Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are present in variable number in most human cell types and have been linked to various cellular functions, including roles as depots for DNA repair proteins. Here, we show that treatment of human cells with DNA methylating agents leads to redistribution of PML from NBs to a diffuse nuclear localization. Biochemically, this correlates with a specific reduction of PML levels in the nuclear matrix fraction without affecting total PML levels. Similar results were obtained for the other major PML NB component, the Sp100 protein, indicating that DNA methylating agents lead to a general disassembly of PML NBs. Similar to the dispersal of PML NBs in response to some viral infections, PML redistribution after DNA damage was inhibited by the proteasome inhibitor MG132. We propose that the regulated dispersal of PML NBs may facilitate the enhanced release of DNA repair proteins from NB depots in order to respond adequately to extensive DNA damage.
Conlan
Lindus A
LA
St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
McNees
Carolyn J
CJ
Heierhorst
Jörg
J
D002467:Cell Nucleus / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004249:DNA Damage; D019175:DNA Methylation; D006801:Humans; D009097:Multienzyme Complexes / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex