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2019, Advances in Protein Chemistry and Structural BiologyCitation Excerpt :Once activated, CDK4 and CDK6 deactivate retinoblastoma (pRB), leading to release of E2F transcription factors, which will transactivate multiple cell cycle regulators, including A and E-type cyclins (Ishida et al., 2001; Ren et al., 2002). Subsequent activation of CDKs (Nasmyth, 1993) as well as the Dbf4-dependent kinase (DDK) drives origin firing (Jackson, Pahl, Harrison, Rosamond, & Sclafani, 1993; Kitada, Johnson, Johnston, & Sugino, 1993; Yoon, Loo, & Campbell, 1993). Specifically, binding of Cdc45 to the MCM helix complex requires phosphorylation of MCM2–7 by DDK, while simultaneously, CDK-dependent phosphorylation of Treslin is required for proper initiation of DNA replication (Deegan, Yeeles, & Diffley, 2016; Kumagai, Shevchenko, Shevchenko, & Dunphy, 2010, 2011).
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