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  Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect

Zielinska, A. P., Holubcova, Z., Blayney, M., Elder, K., & Schuh, M. (2015). Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect. eLife, 4: e11389. doi:10.7554/eLife.11389.

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 Urheber:
Zielinska, A. P., Autor
Holubcova, Z., Autor
Blayney, M., Autor
Elder, K., Autor
Schuh, M.1, Autor           
Affiliations:
1Department of Meiosis, MPI for Biophysical Chemistry, Max Planck Society, ou_2205654              

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Schlagwörter: aneuploidy; cell biology; chromosomes; genes; human; human oocytes; kinetochores; maternal age effect; meiosis; mouse
 Zusammenfassung: Aneuploidy in human eggs is the leading cause of pregnancy loss and Down's syndrome. Aneuploid eggs result from chromosome segregation errors when an egg develops from a progenitor cell, called an oocyte. The mechanisms that lead to an increase in aneuploidy with advanced maternal age are largely unclear. Here, we show that many sister kinetochores in human oocytes are separated and do not behave as a single functional unit during the first meiotic division. Having separated sister kinetochores allowed bivalents to rotate by 90 degrees on the spindle and increased the risk of merotelic kinetochore-microtubule attachments. Advanced maternal age led to an increase in sister kinetochore separation, rotated bivalents and merotelic attachments. Chromosome arm cohesion was weakened, and the fraction of bivalents that precociously dissociated into univalents was increased. Together, our data reveal multiple age-related changes in chromosome architecture that could explain why oocyte aneuploidy increases with advanced maternal age.

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Sprache(n): eng - English
 Datum: 2015-12-15
 Publikationsstatus: Online veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.7554/eLife.11389
 Art des Abschluß: -

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Titel: eLife
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Cambridge : eLife Sciences Publications
Seiten: 19 Band / Heft: 4 Artikelnummer: e11389 Start- / Endseite: - Identifikator: Anderer: URL
ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X