Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45.
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.
Wohlschlegel
James A
JA
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Dhar
Suman K
SK
Prokhorova
Tatyana A
TA
Dutta
Anindya
A
Walter
Johannes C
JC
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004527:Egg Proteins / Q000378:metabolism; D020224:Expressed Sequence Tags; D007700:Kinetics; D046911:Macromolecular Substances; D064110:Minichromosome Maintenance Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D018741:Replication Origin / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
C102209:CDC45 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D004527:Egg Proteins; D046911:Macromolecular Substances; C527642:Mcm10 protein, Xenopus; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D004247:DNA; C489404:CDC7 protein, S cerevisiae; C489405:CDC7 protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D064110:Minichromosome Maintenance Proteins