クロマチンのトポロジーの安定化により,ゲノム完整性が確保される
Fena Ochs1, Gopal Karemore1,2, Ezequiel Miron3,4
1Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nature
|October 25, 2019
まとめ
哺乳類の細胞は53BP1とRIF1タンパク質を使用して,DNAの二重鎖の断裂部位で3次元クロマチンのトポロジーを安定させ,ゲノムの完全性と表遺伝情報を保護します.
科学分野:
- 細胞生物学
- ゲノミクス
- 分子生物学
背景:
- DNAの二重鎖断裂 (DSB) はゲノムの完全性を脅かします
- 哺乳類の細胞は,DNAの末端をシールドし,過剰な切除を防ぐために53BP1および関連するタンパク質を使用します.
- このDNA修復経路が3次元核構造に与える影響は 以前は知られていなかった.
研究 の 目的:
- 53BP1-RIF1経路がDSBの3次元核構造にどのように影響し,反映されるかを調査する.
- 53BP1とRIF1がクロマチンのトポロジーを安定させるメカニズムを解明する.
主な方法:
- 超高解像度顕微鏡を用いて,タンパク質の局所化とクロマチンの構造を視覚化しました.
- 主要なタンパク質 (53BP1, RIF1, shieldin) の減量研究が行われました.
- 染色体分解,染色体間空間,DNA修復タンパク質の拡散,DNA末端切除の分析
主要な成果:
- 53BP1とRIF1は,DSBで3Dクロマチンのトポロジーを安定させる機能モジュールを形成する.
- 53BP1はコンパクトなクロマチン領域に蓄積し,RIF1をトポロジカルアソシエイトドメイン (TAD) 境界に誘導する.
- これは53BP1またはRIF1の枯渇に伴い,クロマチンの分解と超切除に繋がる,円形のTADの配列を作り出します.
結論:
- 53BP1-RIF1モジュールは,DNA修復とは無関係にDSB付近の染色体トポロジーを安定させる.
- この安定化には3次元核組織の基本的メカニズムがあり,コヘシン枯渇効果に似ています.
- この経路はDNAの末端を 保護するだけでなく 壊れた場所の表遺伝子の 整合性を守ります
関連する概念動画
Spreading of Chromatin Modifications
9.2K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
9.2K
Duplication of Chromatin Structure
7.1K
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
7.1K
Nucleosome Remodeling
10.7K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
10.7K
The Spindle Assembly Checkpoint
3.6K
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...
3.6K
Euchromatin
8.7K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
8.7K
Heterochromatin
17.7K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
17.7K


