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-Structure paper
タイトル | Structural basis of DNA polymerase θ mediated DNA end joining. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 51, Issue 1, Page 463-474, Year 2023 |
掲載日 | 2023年1月11日 |
著者 | Chuxuan Li / Hanwen Zhu / Shikai Jin / Leora M Maksoud / Nikhil Jain / Ji Sun / Yang Gao / |
PubMed 要旨 | DNA polymerase θ (Pol θ) plays an essential role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. However, the mechanisms by which Pol θ recognizes ...DNA polymerase θ (Pol θ) plays an essential role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. However, the mechanisms by which Pol θ recognizes microhomologous DNA ends and performs low-fidelity DNA synthesis remain unclear. Here, we present cryo-electron microscope structures of the polymerase domain of Lates calcarifer Pol θ with long and short duplex DNA at up to 2.4 Å resolution. Interestingly, Pol θ binds to long and short DNA substrates similarly, with extensive interactions around the active site. Moreover, Pol θ shares a similar active site as high-fidelity A-family polymerases with its finger domain well-closed but differs in having hydrophilic residues surrounding the nascent base pair. Computational simulations and mutagenesis studies suggest that the unique insertion loops of Pol θ help to stabilize short DNA binding and assemble the active site for MMEJ repair. Taken together, our results illustrate the structural basis of Pol θ-mediated MMEJ. |
リンク | Nucleic Acids Res / PubMed:36583344 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.4 - 3.0 Å |
構造データ | EMDB-28075, PDB-8ef9: EMDB-28078, PDB-8efc: EMDB-28084, PDB-8efk: |
化合物 | ChemComp-DGT: ChemComp-MG: ChemComp-DDS: |
由来 |
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キーワード | DNA BINDING PROTEIN/DNA / DNA double-strand break repair / Microhomology-mediated end joining / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex |