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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6288413","sourcedb":"PMC","sourceid":"6288413","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6288413","text":"POLE1 Deficiency Links CDKN1C-IMAGe Syndrome18 with Other Replisome-Associated Disorders\nSchematic of replication initiation (adapted by permission from Gaillard et al.22 copyright 2015 Macmillan Publishers), highlighting the sequential action of replisome-associated proteins, mutation of which causes MGS (blue text) and those that are associated with dwarfism with adrenal insufficiency and/or immune deficiency, including IMAGe syndrome (red text). During replication licensing, MCM helicases (MCM2-7) are loaded at replication origins by the ORC complex (ORC1-6) with CDC6 and CDT1 to form the pre-replicative complex (pre-RC). Subsequently, loading of additional replisome protein occurs, regulated by DDK and CDK kinases, to form the pre-initiation complex (pre-IC), that contains the CMG (CDC45, MCMs, GINS) complex. CDKN1C inhibits CDK activity. In the active replisome, Primase-Pol α initiates DNA synthesis with strands extended by the PCNA-associated DNA polymerases δ and ε. POLE1 and POLE2 are part of the Pol ε holoenzyme.","divisions":[{"label":"p","span":{"begin":0,"end":88}}],"tracks":[{"project":"2_test","denotations":[{"id":"30503519-22634751-2055610","span":{"begin":44,"end":46},"obj":"22634751"},{"id":"30503519-25907220-2055611","span":{"begin":168,"end":170},"obj":"25907220"}],"attributes":[{"subj":"30503519-22634751-2055610","pred":"source","obj":"2_test"},{"subj":"30503519-25907220-2055611","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ece5","default":true}]}]}}