Telomere-independent homologue pairing and checkpoint escape of accessory ring chromosomes in male mouse meiosis.
We analyzed transmission of a ring minichromosome (MC) through mouse spermatogenesis as a monosome and in the presence of a homologue. Mice, either monosomic or disomic for the MC, produced MC+ offspring. In the monosomic condition, most univalents underwent self-synapsis as indicated by STAG3, SCP3, and SCP1 deposition. Fluorescent in situ hybridization and three-dimensional fluorescence microscopy revealed that ring MCs did not participate in meiotic telomere clustering while MC homologues paired at the XY-body periphery. Self-synapsis of MC(s) and association with the XY-body likely allowed them to pass putative pachytene checkpoints. At metaphase I and II, MC kinetochores assembled MAD2 and BUBR1 spindle checkpoint proteins. Unaligned MCs triggered the spindle checkpoint leading to apoptosis of metaphase cells. Other MCs frequently associated with mouse pericentric heterochromatin, which may have allowed them to pass the spindle checkpoint. Our findings indicate a telomere-independent mechanism for pairing of mammalian MCs, illuminate escape routes to meiotic checkpoints, and give clues for genetic engineering of germ line-permissive chromosomal vectors.
Voet
Thierry
T
Human Genome Laboratory, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Belgium.
Liebe
Bodo
B
Labaere
Charlotte
C
Marynen
Peter
P
Scherthan
Harry
H
D000818:Animals; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D005656:Fungal Proteins / Q000378:metabolism; D018816:Genes, cdc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D064246:Mad2 Proteins; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins; D009929:Organ Size; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012303:Ring Chromosomes; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D016615:Telomere / Q000378:metabolism*
C584278:Bub1b protein, mouse; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C577699:Mad2l2 protein, mouse; D009687:Nuclear Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases