Drosophila BubR1 is essential for meiotic sister-chromatid cohesion and maintenance of synaptonemal complex.
The partially conserved Mad3/BubR1 protein is required during mitosis for the spindle assembly checkpoint (SAC). In meiosis, depletion causes an accelerated transit through prophase I and missegregation of achiasmate chromosomes in yeast [1], whereas in mice, reduced dosage leads to severe chromosome missegregation [2]. These observations indicate a meiotic requirement for BubR1, but its mechanism of action remains unknown. We identified a viable bubR1 allele in Drosophila resulting from a point mutation in the kinase domain that retains mitotic SAC activity. In males, we demonstrate a dose-sensitive requirement for BubR1 in maintaining sister-chromatid cohesion at anaphase I, whereas the mutant BubR1 protein localizes correctly. In bubR1 mutant females, we find that both achiasmate and chiasmate chromosomes nondisjoin mostly equationally consistent with a defect in sister-chromatid cohesion at late anaphase I or meiosis II. Moreover, mutations in bubR1 cause a consistent increase in pericentric heterochromatin exchange frequency, and although the synaptonemal complex is set up properly during transit through the germarium, it is disassembled prematurely in prophase by stage 1. Our results demonstrate that BubR1 is essential to maintain sister-chromatid cohesion during meiotic progression in both sexes and for normal maintenance of SC in females.
Malmanche
Nicolas
N
Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.
Owen
Stephanie
S
Gegick
Stephen
S
Steffensen
Soren
S
Tomkiel
John E
JE
Sunkel
Claudio E
CE
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002503:Centromere / Q000502:physiology; D002842:Chromatids / Q000502:physiology*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D005260:Female; D008297:Male; D009630:Nondisjunction, Genetic / Q000502:physiology; D012854:Sister Chromatid Exchange / Q000502:physiology; D013573:Synaptonemal Complex / Q000502:physiology*
C506005:BubR1 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins
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