G-quadruplex-stalled eukaryoticレプリソーム構造は,螺旋的なインチワームDNA転位を明らかにしている
Sahil Batra1, Benjamin Allwein2,3, Charanya Kumar1
1Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
まとめ
DNAのG四重複合体 (G4s) は,CMGヘリゼ内に留まり,複合体を停止することによって,DNA複製を遅らせます. これはDNA転移とゲノム安定のためのインチワームのメカニズムを示しています
科学分野:
- 分子生物学
- 遺伝学
- 構造生物学
背景:
- DNA G四重複 (G4s) は非B型DNA構造である.
- G4はDNA複製を阻害し ゲノムの安定性を脅かします
研究 の 目的:
- G4が複製フォーク停止を引き起こすメカニズムを解明する.
- G4レプリソームの相互作用を特徴づけるため
主な方法:
- 再構成された酵母とヒトのレプリソームは,G4とのフォーク衝突を研究するために使用されました.
- 凍結電子顕微鏡 (Cryo-EM) で,停止したCMG複合体の構造を決定した.
主要な成果:
- リードストランドのテンプレートの単一のG4は,CMGヘリケーゼを停止することによってレプリソームを拘束する.
- クリオ-エム構造は G4が CMGの中央チャネルに収まり 転位を阻害している
- G4は特定の中間物質でCMGを安定させ,螺旋状のインチワーム転移機構を示唆する.
結論:
- G4sは CMGヘリケースを物理的にブロックすることで DNAの複製を止めます
- この研究は,CMGによるDNA転位のための新しいメカニズムを明らかにしています.
- 発見は,正常な状態と混乱した状態のユカリオット複製フォークのダイナミクスを洞察します.
関連する概念動画
The Replisome
32.8K
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...
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...
32.8K
DNA Helicases
21.1K
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...
21.1K
Restarting Stalled Replication Forks
5.7K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.7K
Replication in Eukaryotes
12.9K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
12.9K
The DNA Replication Fork
35.4K
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...
35.4K
Homologous Recombination
50.0K
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...
50.0K


