DNA二重鎖の断裂によって誘発されたアポトーシスにおけるヒストンH1.2の関与
Akimitsu Konishi1, Shigeomi Shimizu, Junko Hirota
1Department of Post-Genomics and Diseases, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Cell
|September 25, 2003
まとめ
ヒストンH1.2は,ミトコンドリアにDNA損傷信号を伝達し,アポトーシスを開始します. このタンパク質は,DNAの二重鎖の断裂後にアポプトシス信号を伝達するために不可欠であり,その発現が減少すると細胞抵抗性を高めます.
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:
- ミトコンドリアへのDNA損傷伝播によるアポプトシス信号は不明である.
- ミトコンドリアの放出因子により,下流破壊プログラムが活性化されます.
研究 の 目的:
- DNA損傷後の核からミトコンドリアにアポプトティック信号を伝達する因子を特定する.
- ヒストンH1.2がアポトーシスにおける役割を調査する.
主な方法:
- ヒストンH1.2をX線照射後のサイトプラズマ因子として特定した.
- 孤立したミトコンドリアからシトクロームcの放出に対するH1.2の影響を評価した.
- 細胞のアポトーシス抵抗性を評価するために,H1.2の発現を減少させた.
- H1.2-欠乏マウスにおけるアポトーシス耐性を調べた.
主要な成果:
- ヒストンH1.2は,他のH1形態は含まないが,シトクロームcの放出を誘導する.
- 減少したH1.2発現は,X線やエトポシド誘発のアポトーシスに対する抵抗性を高めます.
- H1.2 欠乏症は,胸細胞と小腸におけるX線誘発のアポトーシスに対する耐性を授与した.
結論:
- ヒストンH1.2は,DNA二重鎖の断裂後の核からミトコンドリアへのアポプトシ信号の伝達における重要な媒介体である.
- H1.2は,DNA損傷によるアポトーシス経路において特定の役割を果たします.
関連する概念動画
02:04Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
02:36DNA 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...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
02:36DNA 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...