構造的なDNA結合成分を含むヒトのBRCA2複合体は,細胞サイクル進行に影響を与えます
L Y Marmorstein1, A V Kinev, G K Chan
1The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Cell
|February 24, 2001
まとめ
研究者らはBRCA2複合体内のBRCA2関連因子35 (BRAF35) を特定した. このBRAF35タンパク質は,凝縮クロマチンと結合し,乳がんの感受性における細胞サイクル進行を調節する可能性があります.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- 細胞生物学 細胞生物学
背景:
- 人間のBRCA2遺伝子の生殖系統変異は,乳がんのリスクの増加と関連しています.
- BRCA2タンパク質の正確な機能は完全に理解されていません.
- BRCA2欠乏したマウス細胞は染色体異常を示します.
研究 の 目的:
- BRCA2タンパク質の機能を調査する.
- BRCA2複合体の成分を特定するために.
- 細胞プロセスにおけるBRCA2の役割を調査する.
主な方法:
- 大きなBRCA2を含む複合体の分離と特徴付け.
- DNA結合成分の識別と分析,BRAF35.35.
- マウス胚におけるBRAF35 mRNAの発現分析.
- BRAF35/BRCA2局所化を評価するための免疫光染色.
- 機能的役割を研究するために抗体マイクロインジェクション.
主要な成果:
- 2MDaのBRCA2複合体が分離され,BRAF35.5というDNA結合タンパク質を含んでいた.
- BRAF35は,DNA結合のためのHMGドメインと,キネシンのようなコイルドコイルドメインを持っています.
- BRAF35 mRNA発現はBRCA2発現を反映し,増殖している胚組織で最も高い.
- BRAF35/BRCA2複合体は,ミトーシス過程で濃縮クロマチンと局所化する.
- 抗体マイクロインジェクションは,複合体が細胞サイクル進行に影響することを示唆しています.
結論:
- BRAF35は,BRCA2複合体の新しいDNA結合成分である.
- BRCA2/BRAF35複合体はクロマチンと関連しており,細胞サイクル調節に役割を果たす可能性がある.
- BRCA2/BRAF35複合体に関するさらなる研究は,乳がんの感受性の基礎となるメカニズムを明らかにすることができます.
関連する概念動画
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Molecular Factors Affecting Cell Division
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...


