Structural basis of DNA polymerase θ mediated DNA end joining.
Nucleic Acids Res
; 51(1): 463-474, 2023 01 11.
Article
em En
| MEDLINE
| ID: mdl-36583344
ABSTRACT
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 Šresolution. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Perciformes
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DNA Polimerase Dirigida por DNA
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Reparo do DNA por Junção de Extremidades
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article