オーロラBキナーゼによる緊張感知は,生存者ベースのセントロメア局所化とは独立しています
Christopher S Campbell1, Arshad Desai
1Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA.
Nature
|April 23, 2013
まとめ
染色体分離は,適切なスパインドル結合に依存しています. この研究は,セントロメア局所化ではなく,オーロラBキナーゼの活性化が,正しい染色体バイオリエンテーションと分離の鍵であることを示しています.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 精密なゲノム分離には,スパインドルの染色体バイオリエンテーションが必要です.
- 染色体旅客複合体 (CPC) の一部であるオーロラBキナーゼは,バイオオリエンテーションを保証する.
- CPCの内部のセントロメア局所化は,マイクロチューブルの付着部位の張力依存の安定化にとって決定的なと考えられています.
研究 の 目的:
- 染色体分離におけるCPC機能に対する内心セントロメア局在の役割を調査する.
- セントロメア局所化から独立して,クロモソームのバイオリエンテーションに,オーロラBキナーゼの活性化が十分であるかどうかを判断する.
主な方法:
- 芽生える酵母CPCの断片化されたSli15 (INCENP) サブユニットを設計し,内部のセントロメア関連性を排除しました.
- 断絶されたSli15.5でミトーシスと微分化の間に評価された染色体分離.
- 特定のリン酸化条件下 (Cdk1/Cdc28) において,切断されたSli15と全長Sli15の局所化を調査した.
主要な成果:
- 内部セントロメア関連が欠けていた断片化されたSli15は,ミトーシスとマイオシスの両方で適切な染色体分離をサポートしました.
- 断片化されたSli15は,鍵となる内部セントロメアタンパク質 (Bir1,Nbl1,Bub1,Sgo1) のデレーションフェノタイプを抑制した.
- スピンドルマイクロチューブルに局所化された断片化されたSli15と,完全な長さのSli15の早期のマイクロチューブルターゲティングも,生存能力を救いました.
結論:
- CPCの内部センターメアの局所化は,染色体のバイオリエンテーションに不可欠ではありません.
- 染色体または微小管のいずれかにクラスタリングすることによって達成されるオーロラBキナーゼの活性化は,適切な染色体バイオリエンテーションと分離を確保するのに十分です.
関連する概念動画
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
02:17Microtubule Instability
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
02:25Centrosome Duplication
The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each centriole consists of nine sets of three microtubules held together by proteins. The centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix, or pericentriolar material (PCM).
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...
02:17Microtubule Instability
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:15Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)
Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) is an advanced Nuclear Magnetic Resonance (NMR) technique specifically designed to detect and enhance the signals of low-abundance nuclei, such as carbon-13 and nitrogen-15, in small molecules. The fundamental principle behind INEPT is the transfer of polarization from a more abundant and highly polarizable nucleus, typically hydrogen-1, to the low-abundance nucleus of interest. This process effectively boosts the NMR signal of the...