Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45

Mol Cell. 2002 Feb;9(2):233-40. doi: 10.1016/s1097-2765(02)00456-2.

Abstract

Current models suggest that the replication initiation factor Mcm10 is required for association of Mcm2-7 with origins of replication to generate the prereplicative complex (pre-RC). Here we report that Xenopus Mcm10 (XMcm10) is not required for origin binding of XMcm2-7. Instead, the chromatin binding of XMcm10 at the onset of DNA replication requires chromatin-bound XMcm2-7, and it is independent of Cdk2 and Cdc7. In the absence of XMcm10, XCdc45 binding, XRPA binding, and initiation-dependent plasmid supercoiling are blocked. Therefore, XMcm10 performs its function after pre-RC assembly and before origin unwinding. As one of the earliest known pre-RC activation steps, chromatin binding of XMcm10 is an attractive target for regulation by cell cycle checkpoints.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology
  • Chromatin / metabolism
  • DNA / metabolism
  • DNA Replication* / physiology
  • DNA-Binding Proteins / metabolism*
  • Egg Proteins / metabolism
  • Expressed Sequence Tags
  • Kinetics
  • Macromolecular Substances
  • Minichromosome Maintenance Proteins
  • Nuclear Proteins / metabolism
  • Oocytes / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases / physiology
  • Replication Origin / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / metabolism*

Substances

  • CDC45 protein, S cerevisiae
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Egg Proteins
  • Macromolecular Substances
  • Mcm10 protein, Xenopus
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Xenopus Proteins
  • DNA
  • CDC7 protein, S cerevisiae
  • CDC7 protein, Xenopus
  • Protein Serine-Threonine Kinases
  • Minichromosome Maintenance Proteins