Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F18%3A00496890" target="_blank" >RIV/67985904:_____/18:00496890 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.cub.2018.08.052" target="_blank" >http://dx.doi.org/10.1016/j.cub.2018.08.052</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cub.2018.08.052" target="_blank" >10.1016/j.cub.2018.08.052</a>

Result language

angličtina

Original language name

Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis

Original language description

Errors in chromosome segregation during female meiosis I occur frequently, and aneuploid embryos account for 1/3 of all miscarriages in humans [1]. Unlike mitotic cells that require two Aurora kinase (AURK) homologs to help prevent aneuploidy (AURKA and AURKB), mammalian germ cells also require a third (AURKC) [2, 3] AURKA is the spin-dle-pole-associated homolog, and AURKB/C are the chromosome-localized homologs. In mitosis, AURKB has essential roles as the catalytic subunit of the chromosomal passenger complex (CPC), regulating chromosome alignment, kinetochore-microtubule attachments, cohesion, the spindle assembly checkpoint, and cytokinesis [4, 5]. In mouse oocyte meiosis, AURKC takes over as the predominant CPC kinase [6], although the requirement for AURKB remains elusive [7]. In the absence of AURKC, AURKB compensates, making defining potential non-overlapping functions difficult [6, 8]. To investigate the role(s) of AURKB and AURKC in oocytes, we analyzed oocyte-specific Aurkb and Aurkc single- and double-knockout (KO) mice. Surprisingly, we find that double KO female mice are fertile. We demonstrate that, in the absence of AURKC, AURKA localizes to chromosomes in a CPC-dependent manner. These data suggest that AURKC prevents AURKA from localizing to chromosomes by competing for CPC binding. This competition is important for adequate spindle length to support meiosis I. We also describe a unique requirement for AURKB to negatively regulate AURKC to prevent aneuploidy. Together, our work reveals oocyte-specific roles for the AURKs in regulating each other's localization and activity. This inter-kinase regulation is critical to support wild-type levels of fecundity in female mice.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/LO1609" target="_blank" >LO1609: Models of the Serious Human Diseases: Traumatic Spinal Cord Injury, Huntington’s Disease, Melanoma and Infertility</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Current Biology

ISSN

0960-9822

e-ISSN

—

Volume of the periodical

28

Issue of the periodical within the volume

21

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

3458-3468

UT code for WoS article

000449621400029

EID of the result in the Scopus database

2-s2.0-85056155826