Inhibition of DNA binding of MCM2-7 complex by phosphorylation with cyclin-dependent kinases.

摘要: Cyclin-dependent kinase (CDK) that plays a central role in preventing re-replication of DNA phosphorylates several replication proteins to inactivate them. MCM4 MCM2-7 and RPA2 RPA are phosphorylated with CDK vivo. There inversed correlations between the phosphorylation these their chromatin binding. Here, we examined vitro human MCM2-7, RPA, TRESLIN, CDC45 RECQL4 CDK2/cyclinE, CDK2/cyclinA, CDK1/cyclinB, CHK1, CHK2 CDC7/DBF4 kinases. MCM4, RPA2, TRESLIN were CDKs. Effect by CDK2/cyclinA on DNA-binding abilities was gel-shift analysis. The did not affect its ability but inhibited MCM2-7. Change six amino acids serine threonine alanines amino-terminal region rendered mutant insensitive inhibition CDK. These biochemical data suggest at sites direct dislodging from and/or re-loading complex chromatin.