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Molecules involved in DNA replication
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Molecular Interaction Map of modulation after inhibition of replication

Modulation of molecular interactions after inhibition of replication elongation

Mirit Aladjem, Stephania Pasa, Yves Pommier and Kurt W. Kohn
Implemented by : Margot Sunshine, Hong Cao and David Kane
During DNA synthesis, licensed replication origins require the activity of two sets of kinases, DDKs (hsk1/dbf4) and CDKs (Cdk1 or Cdk2). Inhibition of DNA replication activates the ATR kinase that phosphorylates and activates CHK1. Activation of the CHK1 kinase leads to an inhibitory phosphorylation of CDC 25A and a stimulating phosphorylation of wee1. Wee1 kinase facilitates an inhibitory phosphorylation on CDKs; CDC25A phosphorylation inhibits CDC25A and does not allow the removal of the inhibitory phosphorylation. Both phosphorylations therefore result in cyclin dependent kinases remaining in a phosphorylated, inactive stage. At this stage, CDKs cannot mediate initiation of DNA replication on licensed DNA.
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