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极光激酶B和极光激酶C在两个染色体区域的聚集协同维持染色体排列,并防止哺乳动物卵母细胞第二次减数分裂时出现非整倍体。

Aurora B and Aurora C pools at two chromosomal regions collaboratively maintain chromosome alignment and prevent aneuploidy at the second meiotic division in mammalian oocytes.

作者信息

Kouznetsova Anna, Valentiniene Sonata, Liu Jian-Guo, Kitajima Tomoya S, Brismar Hjalmar, Höög Christer

机构信息

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

出版信息

Front Cell Dev Biol. 2024 Sep 17;12:1470981. doi: 10.3389/fcell.2024.1470981. eCollection 2024.

DOI:10.3389/fcell.2024.1470981
PMID:39355122
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11442388/
Abstract

Correct chromosome segregation is essential to preserve genetic integrity. The two protein kinases, Aurora B and its meiotic homolog Aurora C, regulate attachments between chromosomal kinetochores and microtubules, thereby contributing to the accuracy of the chromosome segregation process. Here we performed a detailed examination of the localization and activity of Aurora B/C kinases, their partner Incenp and the kinetochore target Hec1, during the second meiotic division in mouse oocytes. We found that a majority of Aurora B and C changed their localization from the outer kinetochore region of chromosomes at prometaphase II to an inner central region localized between sister centromeres at metaphase II. Depletion of the Aurora B/C pool at the inner central region using the haspin kinase inhibitor 5-iodotubercidin resulted in chromosome misalignments at the metaphase II stage. To further understand the role of the Aurora B/C pool at the central region, we examined the behaviour of single chromatids, that lack a central Aurora B/C pool but retain Aurora B/C at the outer kinetochores. We found that kinetochore-microtubule attachments at single chromatids were corrected at both prometaphase II and metaphase II stages, but that single chromatids compared to paired chromatids were more prone to misalignments following treatment of oocytes with the Aurora B/C inhibitory drugs AZD1152 and GSK1070916. We conclude that the Aurora B/C pool at the inner central region stabilizes chromosome alignment during metaphase II arrest, while Aurora B/C localized at the kinetochore assist in re-establishing chromosome positioning at the metaphase plate if alignment is lost. Collaboratively these two pools prevent missegregation and aneuploidy at the second meiotic division in mammalian oocytes.

摘要

正确的染色体分离对于保持遗传完整性至关重要。两种蛋白激酶,即极光激酶B及其减数分裂同源物极光激酶C,调节染色体动粒与微管之间的附着,从而有助于染色体分离过程的准确性。在此,我们对小鼠卵母细胞第二次减数分裂过程中极光激酶B/C、其伴侣Incenp和动粒靶点Hec1的定位及活性进行了详细研究。我们发现,大多数极光激酶B和C的定位从减数分裂中期II染色体的外动粒区域转变为减数分裂中期II姐妹着丝粒之间的内部中央区域。使用组蛋白H3激酶抑制剂5-碘结核菌素耗尽内部中央区域的极光激酶B/C库会导致减数分裂中期II阶段染色体排列错误。为了进一步了解中央区域极光激酶B/C库的作用,我们研究了单个染色单体的行为,这些染色单体缺乏中央极光激酶B/C库,但在外动粒处保留了极光激酶B/C。我们发现,单个染色单体的动粒-微管附着在减数分裂中期II和中期II阶段都能得到纠正,但与配对染色单体相比,在用极光激酶B/C抑制药物AZD1152和GSK1070916处理卵母细胞后,单个染色单体更容易出现排列错误。我们得出结论,内部中央区域极光激酶B/C库在减数分裂中期II停滞期间稳定染色体排列,而动粒处定位的极光激酶B/C则在排列丢失时协助在中期板重新建立染色体定位。这两个库协同作用可防止哺乳动物卵母细胞第二次减数分裂时出现错误分离和非整倍体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/1331fd644782/fcell-12-1470981-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/a3f2397f4abc/fcell-12-1470981-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/025373123e2d/fcell-12-1470981-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/1331fd644782/fcell-12-1470981-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/a3f2397f4abc/fcell-12-1470981-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/025373123e2d/fcell-12-1470981-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a21/11442388/1331fd644782/fcell-12-1470981-g003.jpg

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本文引用的文献

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Aurora kinases: Generators of spatial control during mitosis.极光激酶:有丝分裂期间空间控制的产生者。
Front Cell Dev Biol. 2023 Mar 13;11:1139367. doi: 10.3389/fcell.2023.1139367. eCollection 2023.
2
Distinct Aurora B pools at the inner centromere and kinetochore have different contributions to meiotic and mitotic chromosome segregation.在有丝分裂和减数分裂中,内着丝粒和动粒处不同的 Aurora B 聚集体对染色体分离有不同的贡献。
Mol Biol Cell. 2023 May 1;34(5):ar43. doi: 10.1091/mbc.E23-01-0014. Epub 2023 Mar 15.
3
Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly.
微管在动粒和染色体驱动下形成束状,促进纺锤体组装。
Nat Commun. 2022 Nov 27;13(1):7307. doi: 10.1038/s41467-022-34957-4.
4
Haspin participates in AURKB recruitment to centromeres and contributes to chromosome congression in male mouse meiosis.Haspin 参与 AURKB 在着丝粒处的招募,并有助于雄性小鼠减数分裂中染色体的向心移动。
J Cell Sci. 2022 Jul 1;135(13). doi: 10.1242/jcs.259546. Epub 2022 Jul 11.
5
The right place at the right time: Aurora B kinase localization to centromeres and kinetochores.在适当的时间出现在适当的位置:极光激酶 B 向着着丝粒和动粒的定位。
Essays Biochem. 2020 Sep 4;64(2):299-311. doi: 10.1042/EBC20190081.
6
Establishing correct kinetochore-microtubule attachments in mitosis and meiosis.在有丝分裂和减数分裂中建立正确的动粒-微管连接。
Essays Biochem. 2020 Sep 4;64(2):277-287. doi: 10.1042/EBC20190072.
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J Cell Biol. 2020 Mar 2;219(3). doi: 10.1083/jcb.201905144.
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Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis.解析 Haspin 和 Bub1 在有丝分裂过程中对 Aurora B 功能的贡献。
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Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation.着丝粒定位的极光激酶B对于染色体分离的准确性是必需的。
J Cell Biol. 2020 Feb 3;219(2). doi: 10.1083/jcb.201907092.
10
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