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J Biol Chem. 2013 May 3;288(18):12742-52. doi: 10.1074/jbc.M112.398073. Epub 2013 Mar 19.

The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity.

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Istituto di Biochimica delle Proteine, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy.


The Tim-Tipin complex plays an important role in the S phase checkpoint and replication fork stability in metazoans, but the molecular mechanism underlying its biological function is poorly understood. Here, we present evidence that the recombinant human Tim-Tipin complex (and Tim alone) markedly enhances the synthetic activity of DNA polymerase ε. In contrast, no significant effect on the synthetic ability of human DNA polymerase α and δ by Tim-Tipin was observed. Surface plasmon resonance measurements and co-immunoprecipitation experiments revealed that recombinant DNA polymerase ε directly interacts with either Tim or Tipin. In addition, the results of DNA band shift assays suggest that the Tim-Tipin complex (or Tim alone) is able to associate with DNA polymerase ε bound to a 40-/80-mer DNA ligand. Our results are discussed in view of the molecular dynamics at the human DNA replication fork.


DNA Damage; DNA Enzymes; DNA Polymerase; DNA Repair; DNA Replication; DNA-Protein Interaction; Fork Protection Complex; Tim-Tipin Complex

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