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


Aria, Valentina; De Felice, Mariarita; Di Perna, Roberta; Uno, Shuji; Masai, Hisao; Syväoja, Juhani E; van Loon, Barbara; Hübscher, Ulrich; Pisani, Francesca M (2013). The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity. Journal of Biological Chemistry, 288(18):12742-12752.

Abstract

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.

Abstract

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
Date:2013
Deposited On:28 Jan 2014 14:28
Last Modified:04 Aug 2017 19:19
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Aria, Valentina; De Felice, Mariarita; Di Perna, Roberta; Uno, Shuji; Masai, Hisao; Syväoja, Juhani E; van Loon, Barbara; Hübscher, Ulrich; Pisani, Francesca M (2013). The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity. Journal of Biological Chemistry, 288(18):12742-12752. © the American Society for Biochemistry and Molecular Biology.
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.M112.398073
PubMed ID:23511638

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