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 (PubMed:
11535615, PubMed:
12446774, PubMed:
12399544, PubMed:
14559997, PubMed:
14988723, PubMed:
15311285, PubMed:
15665856, PubMed:
15650047, PubMed:
32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:
11535615, PubMed:
12446774, PubMed:
12399544, PubMed:
14559997, PubMed:
14988723, PubMed:
15311285, PubMed:
15665856, PubMed:
15650047). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:
11535615, PubMed:
12446774, PubMed:
12399544, PubMed:
14559997, PubMed:
14988723, PubMed:
15311285, PubMed:
15665856, PubMed:
15650047). Recognizes the substrate consensus sequence [R-X-X- S/T] (PubMed:
11535615, PubMed:
12446774, PubMed:
12399544, PubMed:
14559997, PubMed:
14988723, PubMed:
15311285, PubMed:
15665856, PubMed:
15650047). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:
9278511, PubMed:
12676583, PubMed:
14681206, PubMed:
12676925, PubMed:
12759351, PubMed:
19734889, PubMed:
14559997). 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 (PubMed:
9278511). Phosphorylation of CDC25A at 'Ser- 76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:
9278511, PubMed:
12676583, PubMed:
14681206, PubMed:
12676925, PubMed:
12759351, PubMed:
19734889). 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 (PubMed:
9278511, PubMed:
19734889, PubMed:
20090422). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:
9278511). Also phosphorylates NEK6 (PubMed:
18728393). 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 (PubMed:
15665856). 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 (PubMed:
10673501, PubMed:
15659650, PubMed:
16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:
17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:
12660173, PubMed:
12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:
12660173, PubMed:
12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:
18451105). 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 (PubMed:
17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:
31316063). 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 (PubMed:
33108758).
