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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/LO1609" target="_blank" >LO1609: Modely závažných lidských onemocnění: Traumatické poškození míchy, Huntingtonova choroba, melanom a neplodnost</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Current Biology

ISSN

0960-9822

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

21

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

3458-3468

Kód UT WoS článku

000449621400029

EID výsledku v databázi Scopus

2-s2.0-85056155826