Fig. 6. (A) In response to DNA damage (or replication inhibition - not shown), Rad3-Rad26 is loaded onto the DNA. The 9-1-1 complex is loaded independently of Rad3-Rad26 by Rad17, which is itself constitutively DNA associated. Rad4, which may be constitutively chromatin associated or loaded in response to DNA damage, makes contact with Rad3-Rad26 (possibly by associating with both proteins) and Rad17. Rad4 anchors Crb2 and, indirectly, Chk1 to the region. It is anticipated that Rad4 plays a similar role in tethering Cds1 to the checkpoint complex in the event of an inhibition of DNA replication. (B) In the absence of Rad4, Rad3 and 9-1-1 are loaded normally, but Chk1 (or Cds1 in the case of replication inhibition) is not available for phosphorylation or activation, whereas Rad9 and Hus1 are.

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