Gene interactions and pathways from curated databases and text-mining
Mol Cell 2000, PMID: 10882098

Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.

Walter, J; Newport, J

We report that a plasmid replicating in Xenopus egg extracts becomes negatively supercoiled during replication initiation. Supercoiling requires the initiation factor Cdc45, as well as the single-stranded DNA-binding protein RPA, and therefore likely represents origin unwinding. When unwinding is prevented, Cdc45 binds to chromatin whereas DNA polymerase alpha does not, indicating that Cdc45, RPA, and DNA polymerase alpha bind chromatin sequentially at the G1/S transition. Whereas the extent of origin unwinding is normally limited, it increases dramatically when DNA polymerase alpha is inhibited, indicating that the helicase that unwinds DNA during initiation can become uncoupled from the replication fork. We discuss the implications of these results for the location of replication start sites relative to the prereplication complex.

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Text Mining Data

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Manually curated Databases

  • Reactome Reaction: MCM7 → RPA2 (indirect_complex)
  • Reactome Reaction: RPA3 → MCM8 (reaction)
  • Reactome Reaction: CDC6 → RPA4 (reaction)
  • Reactome Reaction: ORC1 → RPA2 (reaction)
  • Reactome Reaction: POLE2 → PRIM2 (reaction)
  • Reactome Reaction: RPA3 → MCM10 (indirect_complex)
  • Reactome Reaction: RPA2 → MCM10 (indirect_complex)
  • Reactome Reaction: MCM3 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM6 → RPA3 (reaction)
  • Reactome Reaction: CDC7 → RPA3 (indirect_complex)
  • Reactome Reaction: RPA1 → MCM8 (reaction)
  • Reactome Reaction: DBF4 → RPA1 (indirect_complex)
  • Reactome Reaction: MCM6 → RPA4 (indirect_complex)
  • Reactome Reaction: POLE2 → POLA1 (reaction)
  • Reactome Reaction: DBF4 → RPA4 (reaction)
  • Reactome Reaction: ORC2 → RPA3 (reaction)
  • Reactome Reaction: CDC45 → RPA4 (indirect_complex)
  • Reactome Reaction: ORC3 → RPA1 (indirect_complex)
  • Reactome Reaction: ORC3 → RPA2 (reaction)
  • Reactome Reaction: ORC5 → RPA1 (reaction)
  • Reactome Reaction: DBF4 → RPA2 (reaction)
  • Reactome Reaction: MCM4 → RPA4 (reaction)
  • Reactome Reaction: MCM6 → RPA1 (indirect_complex)
  • Reactome Reaction: POLA1 → POLE (indirect_complex)
  • Reactome Reaction: MCM5 → RPA1 (indirect_complex)
  • Reactome Reaction: ORC1 → RPA2 (indirect_complex)
  • Reactome Reaction: ORC4 → RPA4 (indirect_complex)
  • Reactome Reaction: CDC6 → RPA4 (indirect_complex)
  • Reactome Reaction: POLE → PRIM2 (indirect_complex)
  • Reactome Reaction: ORC3 → RPA3 (reaction)
  • Reactome Reaction: MCM3 → RPA3 (indirect_complex)
  • Reactome Reaction: MCM3 → RPA4 (indirect_complex)
  • Reactome Reaction: RPA1 → MCM10 (indirect_complex)
  • Reactome Reaction: RPA4 → MCM10 (indirect_complex)
  • Reactome Reaction: CDC6 → RPA2 (reaction)
  • Reactome Reaction: CDK2 → RPA4 (reaction)
  • Reactome Reaction: CDC6 → RPA2 (indirect_complex)
  • Reactome Reaction: CDC45 → RPA3 (indirect_complex)
  • Reactome Reaction: CDC45 → RPA1 (indirect_complex)
  • Reactome Reaction: MCM4 → RPA2 (reaction)
  • Reactome Reaction: CDK2 → RPA1 (indirect_complex)
  • Reactome Reaction: CDC6 → RPA3 (indirect_complex)
  • Reactome Reaction: RPA3 → MCM10 (reaction)
  • Reactome Reaction: MCM7 → RPA1 (reaction)
  • Reactome Reaction: ORC3 → RPA4 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA2 (indirect_complex)
  • Reactome Reaction: CDC7 → RPA1 (reaction)
  • Reactome Reaction: POLE2 → PRIM1 (reaction)
  • Reactome Reaction: DBF4 → RPA3 (indirect_complex)
  • Reactome Reaction: MCM2 → RPA2 (reaction)
  • Reactome Reaction: MCM6 → RPA1 (reaction)
  • Reactome Reaction: ORC2 → RPA1 (indirect_complex)
  • Reactome Reaction: CDC7 → RPA2 (reaction)
  • Reactome Reaction: ORC2 → RPA2 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA3 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA1 (indirect_complex)
  • Reactome Reaction: RPA2 → MCM10 (reaction)
  • Reactome Reaction: MCM2 → RPA1 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA4 (reaction)
  • Reactome Reaction: ORC3 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM3 → RPA4 (reaction)
  • Reactome Reaction: RPA3 → MCM8 (indirect_complex)
  • Reactome Reaction: POLE2 → PRIM2 (indirect_complex)
  • Reactome Reaction: ORC2 → RPA2 (reaction)
  • Reactome Reaction: ORC4 → RPA4 (reaction)
  • Reactome Reaction: MCM5 → RPA2 (reaction)
  • Reactome Reaction: RPA1 → MCM10 (reaction)
  • Reactome Reaction: CDC7 → RPA4 (indirect_complex)
  • Reactome Reaction: MCM3 → RPA2 (reaction)
  • Reactome Reaction: RPA4 → MCM10 (reaction)
  • Reactome Reaction: CDK2 → RPA2 (reaction)
  • Reactome Reaction: CDC45 → RPA1 (reaction)
  • Reactome Reaction: ORC4 → RPA2 (indirect_complex)
  • Reactome Reaction: ORC4 → RPA3 (reaction)
  • Reactome Reaction: POLE2 → PRIM1 (indirect_complex)
  • Reactome Reaction: CDK2 → RPA3 (reaction)
  • Reactome Reaction: MCM2 → RPA4 (indirect_complex)
  • Reactome Reaction: ORC3 → RPA1 (reaction)
  • Reactome Reaction: MCM4 → RPA4 (indirect_complex)
  • Reactome Reaction: POLE2 → POLA2 (indirect_complex)
  • Reactome Reaction: MCM3 → RPA1 (reaction)
  • Reactome Reaction: POLA2 → POLE (reaction)
  • Reactome Reaction: RPA2 → MCM8 (reaction)
  • Reactome Reaction: POLA1 → POLE (reaction)
  • Reactome Reaction: MCM4 → RPA1 (reaction)
  • Reactome Reaction: MCM7 → RPA4 (reaction)
  • Reactome Reaction: CDC7 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM7 → RPA1 (indirect_complex)
  • Reactome Reaction: CDC7 → RPA1 (indirect_complex)
  • Reactome Reaction: DBF4 → RPA4 (indirect_complex)
  • Reactome Reaction: ORC2 → RPA4 (indirect_complex)
  • Reactome Reaction: CDC7 → RPA4 (reaction)
  • Reactome Reaction: DBF4 → RPA1 (reaction)
  • Reactome Reaction: DBF4 → RPA3 (reaction)
  • Reactome Reaction: ORC4 → RPA3 (indirect_complex)
  • Reactome Reaction: ORC1 → RPA1 (reaction)
  • Reactome Reaction: ORC5 → RPA4 (reaction)
  • Reactome Reaction: ORC1 → RPA1 (indirect_complex)
  • Reactome Reaction: RPA2 → MCM8 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA2 (reaction)
  • Reactome Reaction: POLE → PRIM2 (reaction)
  • Reactome Reaction: ORC6 → RPA1 (reaction)
  • Reactome Reaction: CDC6 → RPA1 (indirect_complex)
  • Reactome Reaction: RPA4 → MCM8 (indirect_complex)
  • Reactome Reaction: CDK2 → RPA4 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA3 (reaction)
  • Reactome Reaction: CDC45 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM7 → RPA2 (reaction)
  • Reactome Reaction: POLE → PRIM1 (reaction)
  • Reactome Reaction: CDK2 → RPA3 (indirect_complex)
  • Reactome Reaction: ORC5 → RPA3 (indirect_complex)
  • Reactome Reaction: MCM5 → RPA4 (reaction)
  • Reactome Reaction: MCM5 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM5 → RPA1 (reaction)
  • Reactome Reaction: DBF4 → RPA2 (indirect_complex)
  • Reactome Reaction: POLA2 → POLE (indirect_complex)
  • Reactome Reaction: CDC6 → RPA3 (reaction)
  • Reactome Reaction: MCM7 → RPA3 (indirect_complex)
  • Reactome Reaction: ORC4 → RPA2 (reaction)
  • Reactome Reaction: ORC5 → RPA2 (indirect_complex)
  • Reactome Reaction: CDC45 → RPA4 (reaction)
  • Reactome Reaction: RPA4 → MCM8 (reaction)
  • Reactome Reaction: CDK2 → RPA1 (reaction)
  • Reactome Reaction: MCM7 → RPA4 (indirect_complex)
  • Reactome Reaction: ORC6 → RPA4 (indirect_complex)
  • Reactome Reaction: MCM3 → RPA1 (indirect_complex)
  • Reactome Reaction: ORC4 → RPA1 (reaction)
  • Reactome Reaction: ORC1 → RPA3 (indirect_complex)
  • Reactome Reaction: MCM5 → RPA3 (reaction)
  • Reactome Reaction: MCM3 → RPA3 (reaction)
  • Reactome Reaction: POLE → PRIM1 (indirect_complex)
  • Reactome Reaction: MCM6 → RPA3 (indirect_complex)
  • Reactome Reaction: MCM2 → RPA4 (reaction)
  • Reactome Reaction: CDC6 → RPA1 (reaction)
  • Reactome Reaction: ORC1 → RPA4 (reaction)
  • Reactome Reaction: MCM2 → RPA3 (indirect_complex)
  • Reactome Reaction: CDK2 → RPA2 (indirect_complex)
  • Reactome Reaction: ORC2 → RPA4 (reaction)
  • Reactome Reaction: MCM5 → RPA4 (indirect_complex)
  • Reactome Reaction: MCM2 → RPA1 (reaction)
  • Reactome Reaction: ORC5 → RPA2 (reaction)
  • Reactome Reaction: MCM7 → RPA3 (reaction)
  • Reactome Reaction: MCM2 → RPA3 (reaction)
  • Reactome Reaction: ORC5 → RPA3 (reaction)
  • Reactome Reaction: CDC7 → RPA3 (reaction)
  • Reactome Reaction: ORC3 → RPA3 (indirect_complex)
  • Reactome Reaction: POLE2 → POLA1 (indirect_complex)
  • Reactome Reaction: MCM5 → RPA3 (indirect_complex)
  • Reactome Reaction: MCM4 → RPA3 (indirect_complex)
  • Reactome Reaction: ORC1 → RPA3 (reaction)
  • Reactome Reaction: ORC5 → RPA1 (indirect_complex)
  • Reactome Reaction: MCM4 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM6 → RPA4 (reaction)
  • Reactome Reaction: MCM6 → RPA2 (reaction)
  • Reactome Reaction: ORC5 → RPA4 (indirect_complex)
  • Reactome Reaction: MCM2 → RPA2 (indirect_complex)
  • Reactome Reaction: ORC3 → RPA4 (reaction)
  • Reactome Reaction: ORC1 → RPA4 (indirect_complex)
  • Reactome Reaction: MCM4 → RPA3 (reaction)
  • Reactome Reaction: ORC2 → RPA3 (indirect_complex)
  • Reactome Reaction: ORC2 → RPA1 (reaction)
  • Reactome Reaction: MCM6 → RPA2 (indirect_complex)
  • Reactome Reaction: MCM4 → RPA1 (indirect_complex)
  • Reactome Reaction: POLE2 → POLA2 (reaction)
  • Reactome Reaction: ORC4 → RPA1 (indirect_complex)
  • Reactome Reaction: CDC45 → RPA3 (reaction)
  • Reactome Reaction: RPA1 → MCM8 (indirect_complex)
  • Reactome Reaction: CDC45 → RPA2 (reaction)
In total, 84 gene pairs are associated to this article in curated databases