Molecules involved in DNA 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.