Cdk1 ‐interacting protein Cip1 is regulated by the S phase checkpoint in response to genotoxic stress

In this study, we place Cip1, a recently identified Cdk1 inhibitor (CKI), under the regulation of Mec1 and Rad53 in response to genotoxic stress. Cip1 accumulates dramatically in a Mec1‐ and Rad53‐dependent manner upon replication stress. This increase requires the activity of MBF, but not the transcriptional activator kinase Dun1. At the protein level, stabilization of replication stress‐induced Cip1 requires continued de novo protein synthesis. In addition, Cip1 is phosphorylated at an S/TQ motif in a Mec1‐dependent manner. Deletion of Cip1 affects proliferation in hydroxyurea‐containing plates. Significantly, the sensitivity is increased when the dosage of the G1 cyclin CLN2 is increased, compatible to a role of Cip1 as a G1‐cyclin‐dependent kinase inhibitor. In all, our results place Cip1 under the S phase checkpoint response to genotoxic stress. Furthermore, Cip1 plays a significant role to preserve viability in response to insults that threaten chromosome replication.

We place Cip1, a recently identified Cdk1 inhibitor (CKI), under the regulation of Mec1 and Rad53 in response to genotoxic stress. Cip1 accumulates dramatically in a Mec1‐ and Rad53‐dependent manner upon replication stress. Cip1 is phosphorylated at an S/TQ motif in a Mec1‐dependent manner.

Source: Genes to Cells - July 1, 2017 Category: Genetics & Stem Cells Authors: Ze Zhang, Ping Ren, Ajay A. Vashisht, James A. Wohlschlegel, David G. Quintana, Fanli Zeng Tags: Original Article Source Type: research