Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (    ). May also negatively regulate cell cycle progression during unperturbed cell cycles (   , ). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (   , ). Recognizes the substrate consensus sequence [R-X-X-S/T] (   , ). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (   ). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C . Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (  , ). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A ( ). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression . Also phosphorylates NEK6 . Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination . Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation ( ). Also promotes repair of DNA cross-links through phosphorylation of FANCE . Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (, ). This may enhance chromatin assembly both in the presence or absence of DNA damage (, ). May also play a role in replication fork maintenance through regulation of PCNA . May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest . Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin . Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity .
Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.
Subcellular locations: Nucleus, Chromosome, Cytoplasm, Cytoplasm, Cytoskeleton, Microtubule organizing center, Centrosome
Nuclear export is mediated at least in part by XPO1/CRM1 . Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B . Proteolytic cleavage at the C-terminus by SPRTN promotes removal from chromatin .
Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon.