余分なセンターソームと染色体の不安定性を結びつけるメカニズムです
Neil J Ganem1, Susana A Godinho, David Pellman
1Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|June 10, 2009
まとめ
余分なセンターソームは,多極細胞分裂ではなく,双極細胞分裂の間に染色体分離を促すことで,がんにおける染色体不安定性 (CIN) を引き起こします. これは,余分なセンターソームと腫瘍の発達を結びつける重要なメカニズムを明確にします.
科学分野:
- 細胞生物学 細胞生物学
- がん研究 がん研究
- 遺伝学 遺伝学とは
背景:
- 染色体不安定性 (CIN) は,多くの腫瘍に共通する特徴である.
- CINはしばしば,余分なセンターソームの存在と相関する.
- エクストラセンターソームとCINのメカニズム的な関連は不明のままである.
研究 の 目的:
- エクストラセントロソームと染色体不安定性 (CIN) のメカニズム的な関連性を調査する.
- エクストラセンターソームが多極分裂または他のメカニズムを通じて直接CINを引き起こすかどうかを判断する.
- 癌細胞における余分なセンターソームから生じる特定のミトーシス欠陥を解明する.
主な方法:
- 異なるセンターソーム数を持つ細胞の長期生体細胞イメージング.
- センターソーム数だけによって異なる細胞系を生成する.
- 多極および双極分裂を含む細胞分裂パターンの分析,および染色体分離精度.
主要な成果:
- 余分なセンターソームを持つ細胞は,多極分裂を経験することはめったになく,その子孫はしばしば不活力となる.
- 余分なセンターソームを持つCIN細胞は,主に双極分裂の際に染色体の遅延が増加することを表しています.
- 余分なセンターソームだけでは,一時的な多極スパインドル中間経由による双極分裂の間に染色体分離を誤るのに十分である.
結論:
- 余分なセンターソームは,主に多極分化ではなく双極分化における染色体分離を促すことによって染色体不安定性 (CIN) を引き起こします.
- 暫定的な多極スパインドルの中間は,メロテリックの固定エラーを許し,CINにつながります.
- このメカニズムは,エクストラセンターソームとCINの間の直接的なリンクを提供し,多くのヒトがんにおけるCINを潜在的に説明します.
関連する概念動画
The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Centrosome 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...
Centrosome 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...
Attachment of Sister Chromatids
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall of a...
Attachment of Sister Chromatids
As cells progress into mitosis, the nuclear envelope breaks down, and the condensed chromosomes are exposed to the array of bipolar microtubules of the mitotic spindle. The kinetochore, a large, disc-shaped protein complex, is present at the centromere region of the sister chromatids and acts as a binding site for the microtubules. Usually, the plus-end of a single microtubule is embedded within the kinetochore. However, some kinetochores first establish lateral contact with the side-wall of a...


