Three-dimensional organization of promyelocytic leukemia nuclear bodies.
Promyelocytic leukemia nuclear bodies (PML-NBs) are mobile subnuclear organelles formed by PML and Sp100 protein. They have been reported to have a role in transcription, DNA replication and repair, telomere lengthening, cell cycle control and tumor suppression. We have conducted high-resolution 4Pi fluorescence laser-scanning microscopy studies complemented with correlative electron microscopy and investigations of the accessibility of the PML-NB subcompartment. During interphase PML-NBs adopt a spherical organization characterized by the assembly of PML and Sp100 proteins into patches within a 50- to 100-nm-thick shell. This spherical shell of PML and Sp100 imposes little constraint to the exchange of components between the PML-NB interior and the nucleoplasm. Post-translational SUMO modifications, telomere repeats and heterochromatin protein 1 were found to localize in characteristic patterns with respect to PML and Sp100. From our findings, we derived a model that explains how the three-dimensional organization of PML-NBs serves to concentrate different biological activities while allowing for an efficient exchange of components.
Division of High Resolution Optical Microscopy, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
Marion
M
Lang
Thibaud
T
Jegou
Inn
I
Chung
Karsten
K
Richter
Sandra
S
Münch
Anikó
A
Udvarhelyi
Christoph
C
Cremer
Peter
P
Hemmerich
Johann
J
Engelhardt
Stefan W
SW
Hell
Karsten
K
Rippe
D034961:Antigens, Nuclear / Q000378:metabolism / Q000648:ultrastructure; D001324:Autoantigens / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism* / Q000648:ultrastructure; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000648:ultrastructure; D014452:Ubiquitins / Q000378:metabolism
D034961:Antigens, Nuclear; D001324:Autoantigens; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C066642:SP100 protein, human; C070576:PML protein, human