The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity.
J Biol Chem
; 288(18): 12742-52, 2013 May 03.
Article
em En
| MEDLINE
| ID: mdl-23511638
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Proteínas Nucleares
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Proteínas de Transporte
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Complexos Multiproteicos
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DNA Polimerase II
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article