人間の複製前の複合体は オープン複合体です
Jian Li1, Jiangqing Dong2, Weitao Wang3
1School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Cell
|January 7, 2023
まとめ
ミニクロモソームメンテナンス (MCM) ダブルヘクサマー (DH) が DNA 鎖を溶かして DNA の複製を開始する方法を研究者が発見しました この構造は,ヒト細胞の複製許可に不可欠な初期オープン構造 (IOS) を明らかにします.
科学分野:
- 分子生物学
- 遺伝学
- 生物化学
背景:
- DNA複製の開始は,真核生物の細胞分裂に不可欠である.
- ミニ染色体維持 (MCM) 2-7 ダブルヘクサマー (DH) は,DNA複製を開始するための重要な複合体である.
- MCM-DHが起源DNAを溶かす正確なメカニズムは,ほとんど不明である.
研究 の 目的:
- 複製の開始時にヒトMCM-DH (hMCM-DH) による初期DNA溶解の構造的メカニズムを解明する.
- hMCM-DHが複製の起源で初期オープン構造 (IOS) の形成をどのように促進するのかを理解する.
- DNA複製の認可における IOSの役割を調査する.
主な方法:
- DNAに結合したhMCM-DHの高解像度構造を決定するための冷凍電子顕微鏡 (冷凍-EM).
- DH形成と複製の開始に対するIOSの障害の影響を評価する生化学的測定法.
- hMCM-DHとIOSの分布をゲノム全体にマッピングするゲノム足跡.
主要な成果:
- hMCM-DHの2.59-Åの冷凍-EM構造は,結合DNAを歪める狭い中央チャネルを明らかにした.
- hMCM-DHは,歪んだDNA複合体内の1つの塩基対を分離することによって,初期オープン構造 (IOS) を誘導する.
- IOSの障害は,MCM- DHの形成とその後の複製の開始を著しく阻害する.
- ゲノムマッピングは IOS が初期ゾーンに集まっていることを示し ストキャスティック起源の発射と相関しています
結論:
- hMCM-DHは,DNA結合と初期鎖分離をカップリングする内在的なメカニズムを有し,IOSを形成する.
- このIOSはヒト細胞におけるDNA複製の開始を許可する上で極めて重要です.
- これらの発見は,複製の起源がどのように選択され,開かれるかを理解するための構造的基礎を提供します.
関連する概念動画
03:01The Replisome
34.3K
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...
34.3K
02:31Chromosome Replication
8.9K
Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins. This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
8.9K
00:55DNA Helicases
21.8K
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...
21.8K
01:29Replication in Eukaryotes
14.1K
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...
14.1K
02:31Homologous Recombination
50.8K
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...
50.8K
01:02The DNA Replication Fork
36.3K
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...
36.3K