Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion

During meiotic prophase I, accurate segregation of homologous chromosomes requires the establishment of a chromosomes with a meiosis-specific architecture. Sister chromatid cohesins and the enzyme Topoisomerase II are important components of meiotic chromosome axes, but the relationship of these proteins in the context of meiotic chromosome segregation is poorly defined. Here, we analyzed the role of Topoisomerase II (TOP-2) in the timely release of sister chromatid cohesins during spermatogenesis and oogenesis of Caenorhabditis elegans. We show that there is a different requirement for TOP-2 in meiosis of spermatogenesis and oogenesis. The loss-of-function mutation top-2(it7) results in premature REC-8 removal in spermatogenesis, but not oogenesis. This is due to a failure to maintain the HORMA-domain proteins HTP-1 and HTP-2 (HTP-1/2) on chromosome axes at diakinesis and mislocalization of the downstream components that control sister chromatid cohesion release including Aurora B kinase. In oogenesis, top-2(it7) causes a delay in the localization of Aurora B to oocyte chromosomes but can be rescued through premature activation of the maturation promoting factor via knock-down of the inhibitor kinase WEE-1.3. The delay in Aurora B localization is associated with an increase in the length of diakinesis chromosomes and wee-1.3 RNAi mediated rescue of Auorora B localization in top-2(it7) is associated with a decrease in chromosome length. Our results imply that the sex-specific effects of Topoisomerase II on sister chromatid cohesion release are due to differences in the temporal regulation of meiosis and chromosome structure in late prophase I in spermatogenesis and oogenesis.

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INCENP and Aurora B Promote Meiotic Sister Chromatid Cohesion through Localization of the Shugoshin MEI-S332 in Drosophila

Developmental Cell ◽

10.1016/j.devcel.2006.04.021 ◽

2006 ◽

Vol 11 (1) ◽

pp. 57-68 ◽

Cited By ~ 81

Author(s):

Tamar D. Resnick ◽

David L. Satinover ◽

Fiona MacIsaac ◽

P. Todd Stukenberg ◽

William C. Earnshaw ◽

...

Keyword(s):

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Aurora B ◽

Chromatid Cohesion

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Pericentromeric Sister Chromatid Cohesion Promotes Kinetochore Biorientation

Molecular Biology of the Cell ◽

10.1091/mbc.e09-04-0330 ◽

2009 ◽

Vol 20 (17) ◽

pp. 3818-3827 ◽

Cited By ~ 65

Author(s):

Tessie M. Ng ◽

William G. Waples ◽

Brigitte D. Lavoie ◽

Sue Biggins

Keyword(s):

Protein Kinase ◽

Genetic Analysis ◽

Chromosome Segregation ◽

Sister Chromatid ◽

Budding Yeast ◽

Sister Chromatid Cohesion ◽

Specific Role ◽

Aurora B ◽

Chromatid Cohesion ◽

Yeast Genes

Accurate chromosome segregation depends on sister kinetochores making bioriented attachments to microtubules from opposite poles. An essential regulator of biorientation is the Ipl1/Aurora B protein kinase that destabilizes improper microtubule–kinetochore attachments. To identify additional biorientation pathways, we performed a systematic genetic analysis between the ipl1-321 allele and all nonessential budding yeast genes. One of the mutants, mcm21Δ, precociously separates pericentromeres and this is associated with a defect in the binding of the Scc2 cohesin-loading factor at the centromere. Strikingly, Mcm21 becomes essential for biorientation when Ipl1 function is reduced, and this appears to be related to its role in pericentromeric cohesion. When pericentromeres are artificially tethered, Mcm21 is no longer needed for biorientation despite decreased Ipl1 activity. Taken together, these data reveal a specific role for pericentromeric linkage in ensuring kinetochore biorientation.

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The Aurora kinase Ipl1 maintains the centromeric localization of PP2A to protect cohesin during meiosis

The Journal of Cell Biology ◽

10.1083/jcb.200609153 ◽

2007 ◽

Vol 176 (7) ◽

pp. 911-918 ◽

Cited By ~ 37

Author(s):

Hong-Guo Yu ◽

Douglas Koshland

Keyword(s):

Saccharomyces Cerevisiae ◽

Drosophila Melanogaster ◽

Sister Chromatid ◽

Meiotic Division ◽

Aurora Kinase ◽

Regulatory Subunit ◽

Aurora B ◽

Aurora B Kinase ◽

Spatial Regulation ◽

Chromatid Cohesion

Homologue segregation during the first meiotic division requires the proper spatial regulation of sister chromatid cohesion and its dissolution along chromosome arms, but its protection at centromeric regions. This protection requires the conserved MEI-S332/Sgo1 proteins that localize to centromeric regions and also recruit the PP2A phosphatase by binding its regulatory subunit, Rts1. Centromeric Rts1/PP2A then locally prevents cohesion dissolution possibly by dephosphorylating the protein complex cohesin. We show that Aurora B kinase in Saccharomyces cerevisiae (Ipl1) is also essential for the protection of meiotic centromeric cohesion. Coupled with a previous study in Drosophila melanogaster, this meiotic function of Aurora B kinase appears to be conserved among eukaryotes. Furthermore, we show that Sgo1 recruits Ipl1 to centromeric regions. In the absence of Ipl1, Rts1 can initially bind to centromeric regions but disappears from these regions after anaphase I onset. We suggest that centromeric Ipl1 ensures the continued centromeric presence of active Rts1/PP2A, which in turn locally protects cohesin and cohesion.

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