Chk1 Protein, Human (Active, sf9, GST)

The serine/threonine protein kinase CHK1 is essential for checkpoint-mediated cell cycle arrest and activation of DNA repair caused by DNA damage or unreplicated DNA. It may also negatively regulate cell cycle progression during the normal cell cycle, utilizing various mechanisms to maintain genomic integrity. The kinase recognizes the substrate consensus sequence [R-X-X-S/T] and phosphorylates CDC25A, CDC25B, and CDC25C.
Phosphorylation of CDC25A at specific residues creates binding sites for 14-3-3 proteins, inhibiting their activity, whereas additional phosphorylation promotes proteolysis of CDC25A. Inhibition of CDC25 results in increased tyrosine phosphorylation of CDK-cyclin complexes, arresting cell cycle progression. The kinase also phosphorylates RAD51 and TP53, enhancing DNA repair and promoting cell cycle arrest, respectively. In addition, it regulates chromatin assembly by phosphorylating TLK1 and may be involved in replication fork maintenance through PCNA regulation. It can also phosphorylate histone H3.1, leading to epigenetic repression of certain genes, and phosphorylate RB1 to promote its interaction with E2F transcription factors. In addition, it reduces replication stress and activates the G2/M checkpoint by regulating PABIR1/FAM122A and stabilizing WEE1 levels and activity.