DNA Pol IIによるトランスレション合成に関する構造的洞察
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Building 5, Room B1-03, Bethesda, MD 20892, USA.
Cell
|January 13, 2010
まとめ
エシェリキア・コライのDNAポリメラーゼII (Pol II) と真核生物Rev3は,転移合成を行うB族ポリメラーゼである. DNA Pol IIは,テンプレートスキッピングを含むユニークな構造特性を利用して,DNAの病変を回避し,ゲノムの完全性を維持します.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 遺伝学 遺伝学とは
背景:
- E. coli DNA Pol IIとeukaryotic Rev3を含むB族ポリメラーゼは,DNA修復に不可欠である.
- 高精度複製ポリメラーゼは,損傷または不一致のサイトを過ぎてDNAを複製するのに無効である可能性があります.
- トランスレション合成 (TLS) は,DNAの損傷をバイパスするために特殊なポリメラーゼによって採用されるメカニズムです.
研究 の 目的:
- トランスレション合成を可能にするE. coli DNA Pol IIの生化学的および構造的特性を解明する.
- テンプレートスキッピングを含むDNA Pol IIがDNA損傷をバイパスするメカニズムを理解する.
- DNA Pol IIが,TLS機能で損傷のないDNAの効率的な複製をどのようにバランスさせるかを調査する.
主な方法:
- DNA Pol IIの活性性を特徴付けるための生化学的分析.
- DNA Pol II.の3次元構造を決定するための構造研究.
- 活性サイトとエクソヌクレアースサイト間のDNA基板分割の分析.
主要な成果:
- DNA Pol IIは,直接またはテンプレートスキップを通じて,傷害の過去のプライマーを拡張し,ループされたテンプレートヌクレオチドを小さな空洞に収容することができます.
- 複数のループアウトの代替案に対応する能力は,バイパス合成の変異スペクトルを複雑にします.
- DNA基板の活性部位と校正外核酸部位の間の変化した分割は,TLSを強化する.
- 活性部位から遠く離れた微妙なアミノ酸の変化により,DNA Pol IIは正常DNAを効率的に複製し,同時にTLSを実行します.
結論:
- DNA Pol IIは,効率的な翻訳合成を促進するユニークな構造および生化学的特性を有しています.
- テンプレートスキップと変異した基板分割は,DNA Pol IIがDNA損傷をバイパスすることを可能にする重要なメカニズムです.
- DNA Pol IIは,高精度レプリカとダメージ耐性を有するB族ポリメラーゼを特化したものです.
関連する概念動画
02:10Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
03:01The Replisome
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...
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...
03:01The Replisome
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...
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...
01:59Lagging Strand Synthesis
During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading strand. Replication starts later, occurs more slowly, and proceeds discontinuously on the lagging strand.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
01:59Lagging Strand Synthesis
During replication, the complementary strands in double-stranded DNA are synthesized at different rates. Replication first begins on the leading strand. Replication starts later, occurs more slowly, and proceeds discontinuously on the lagging strand.
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
There are several major differences between synthesis of the leading strand and synthesis of the lagging strand. 1) Leading strand synthesis happens in the direction of replication fork opening, whereas lagging strand synthesis happens in the...
02:40DNA Replication
DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied. After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
DNA replication uses a large number of...
Replication in Prokaryotes
DNA replication uses a large number of...