Has dual roles in initiation of DNA replication, and regulation of checkpoint responses. Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation...[+]

Has dual roles in initiation of DNA replication, and regulation of checkpoint responses. Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages. Necessary for the loading of replication factors onto chromatin, including gemc1, cdc45, DNA polymerases and components of the GINS complex such as ginsl/sld5. Binds chromatin in both S-phase cyclin-dependent kinase (S-CDK)-independent and S-CDK-dependent modes. Chromatin binding is required for the action of S-CDK, which in turn triggers the formation of preinitiation complexes of DNA replication. Its role in checkpoint activation is independent of the DNA replication role. In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the chek1 signaling pathway and block S-phase progression. Increases the kinase activity of atr to numerous substrates, and is required for the phosphorylation of Rad1. [-]

ClinVar, ClinGen, MalaCards, KEGG Disease, DECIPHER, COSMIC, MARRVEL, GTR, DisGeNET, dbVAR, GHR, gnomAD