コンデンシンによる方向性DNAループエクストルーションを駆動するホールド・アンド・フィードメカニズム

Indra A Shaltiel^1,2, Sumanjit Datta^2,3, Léa Lecomte^2,3

¹Department of Biochemistry and Cell Biology, Julius Maximilian University of Würzburg, 97074 Würzburg, Germany.

Science (New York, N.Y.)

|June 2, 2022

まとめ

染色体の構造維持 (SMC) 複合体は,2つの室を使用してDNAループを押し出します. これらの室内のDNAセグメントの方向性はループの流出方向を決定し重要なゲノム構造機構を明らかにします

科学分野:

分子生物学
ゲノミクス
構造生物学

背景:

染色体構造維持 (SMC) タンパク質複合体は,ゲノム構造化に不可欠である.
SMC複合体,特にコンデンシンによるDNAループ挤出の正確な分子機構は,ほとんど不明のままである.

研究の目的:

コンデンシンがDNAループを押し出す分子メカニズムを解明する.
コンデンシンがDNAループエクストルーションで方向性を達成する方法を理解する.

主な方法:

コンデンシン活性を観察するために単一分子画像技術を使用した.
DNA結合中の複合体の高解像度構造を決定するために,冷凍電子顕微鏡 (cryo-EM) が使用されました.

主要な成果:

活性コンデンシン複合体は,DNAループの塩基を捕まえるために2つの別々の室を使用します.
証拠は,第1室のパワーストロークメカニズムを示唆し,ATP結合によって駆動され,SMC-kleisinリングにDNAを供給します.
2つ目の室はアンカーとして機能し,上流のDNAを保持し,方向性のある流出を可能にします.

結論:

コンデンシンは2つの室を持つメカニズムを通して,指向的なDNAループエクストルーダーとして機能します.
SMC複合体内のトポロジカルに結合したDNAセグメントの方向性は,ゲノム維持における基本的プロセスであるDNAループ流出の方向性を決定する.

さらに関連する動画

10:11

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level

Published on: July 26, 2024

1.2K

09:17

Structure-Based Simulation and Sampling of Transcription Factor Protein Movements along DNA from Atomic-Scale Stepping to Coarse-Grained Diffusion

Published on: March 1, 2022

3.3K

関連する概念動画

03:01

The Replisome

35.2K

DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...

35.2K

01:02

The DNA Replication Fork

37.0K

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...

37.0K

00:55

DNA Helicases

22.4K

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...

22.4K

02:15

Condensins

3.7K

Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...

3.7K

01:03

Single-Strand DNA Binding Proteins

15.1K

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...

15.1K

02:02

DNA Topoisomerases

32.2K

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...