دورية أكاديمية
Age-dependent loss of cohesion protection in human oocytes.
العنوان: | Age-dependent loss of cohesion protection in human oocytes. |
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المؤلفون: | Mihalas BP; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK., Pieper GH; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK., Aboelenain M; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK; Theriogenology department, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt., Munro L; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK., Srsen V; Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK., Currie CE; Centre for Mechanochemical Cell Biology & Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK., Kelly DA; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK., Hartshorne GM; Centre for Mechanochemical Cell Biology & Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK; University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK., Telfer EE; Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK; Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK., McAinsh AD; Centre for Mechanochemical Cell Biology & Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry CV4 7AL, UK., Anderson RA; Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK., Marston AL; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK. Electronic address: adele.marston@ed.ac.uk. |
المصدر: | Current biology : CB [Curr Biol] 2024 Jan 08; Vol. 34 (1), pp. 117-131.e5. Date of Electronic Publication: 2023 Dec 21. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: England NLM ID: 9107782 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0445 (Electronic) Linking ISSN: 09609822 NLM ISO Abbreviation: Curr Biol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: London, UK : Current Biology Ltd., c1991- |
مواضيع طبية MeSH: | Cell Cycle Proteins*/genetics , Cell Cycle Proteins*/metabolism , Oocytes*/metabolism, Humans ; Female ; Aged ; Cohesins ; Meiosis ; Centromere/metabolism ; Chromatids/metabolism ; Chromosome Segregation |
مستخلص: | Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis as a common cause. We found that loss of a specific pool of the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon. Our data indicate that SGO2 preserves sister chromatid cohesion in meiosis by protecting a "cohesin bridge" between sister chromatids. In human oocytes, SGO2 localizes to both sub-centromere cups and the pericentromeric bridge, which spans the sister chromatid junction. SGO2 normally colocalizes with cohesin; however, in meiosis II oocytes from older women, SGO2 is frequently lost from the pericentromeric bridge and sister chromatid cohesion is weakened. MPS1 and BUB1 kinase activities maintain SGO2 at sub-centromeres and the pericentromeric bridge. Removal of SGO2 throughout meiosis I by MPS1 inhibition reduces cohesion protection, increasing the incidence of single chromatids at meiosis II. Therefore, SGO2 deficiency in human oocytes can exacerbate the effects of maternal age by rendering residual cohesin at pericentromeres vulnerable to loss in anaphase I. Our data show that impaired SGO2 localization weakens cohesion integrity and may contribute to the increased incidence of aneuploidy observed in human oocytes with advanced maternal age. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
فهرسة مساهمة: | Keywords: MPS1; Meiosis; PP2A; REC8; SGO2; aneuploidy; cohesin; human oocytes; maternal aging; reproductive biology |
المشرفين على المادة: | 0 (Cell Cycle Proteins) 0 (Cohesins) |
تواريخ الأحداث: | Date Created: 20231222 Date Completed: 20240111 Latest Revision: 20240207 |
رمز التحديث: | 20240207 |
DOI: | 10.1016/j.cub.2023.11.061 |
PMID: | 38134935 |
قاعدة البيانات: | MEDLINE |
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