Checkpoint kinase 1 (CHEK1/CHK1) is a serine/threonine kinase that is pivotal in maintaining genomic stability by regulating DNA replication, mitotic progression, and DNA damage response (DDR). Phosphorylation at distinct regulatory sites of CHK1 serves as a central signaling switch that tightly coordinates checkpoint control and DNA repair pathways. However, the broad phosphorylation network associated with the DNA repair pathway and CHK1 phosphorylation remains relatively underexplored, representing an untapped avenue with profound therapeutic potential. To bridge this discovery gap, we systematically analyzed global phosphoproteome datasets to visualize CHK1 phosphosites and their coregulated protein phosphosites, providing new insights into the functional networks governed by DDR signaling. The integrative analysis of 577 qualitative and 120 quantitative cellular phosphoproteomic datasets identified signatures of the CHK1 phosphorylation landscape. Our study visualized a strong co-occurrence of DDR-associated phosphosites in proteins, particularly with S280, and the Ataxia telangiectasia and Rad3-related protein-dependent S317 phosphosites in CHK1 located outside its kinase domain. Their coregulation analysis across CHK1 substrates, kinase regulators, and protein interactions uncovered connectivity between CHK1 phosphosites and DDR regulators. Collectively, our phosphosite-concordance approach reported here provides a regulatory map of CHK1 phosphorylation patterns, uncovering unexplored regulatory layers, and highlights new opportunities to explore mechanistic insights into CHK1 phosphoregulation as a target for therapeutic interventions in cancer.
AbedrabboM, RavidS. Scribble, Lgl1, and Myosin II form a complex in vivo to promote directed cell migration. Mol Biol Cell, 2020; 31(20):2234–2248; doi: 10.1091/mbc.E19-11-0657
2.
AmanJM, ZhuAW, WührM, et al.KINAID: An orthology-based kinase-substrate prediction and analysis tool for phosphoproteomics. Bioinformatics, 2025; 41(5):btaf300; doi: 10.1093/bioinformatics/btaf300
3.
AnandakrishnanM, RossKE, ChenC, et al.KSFinder-a knowledge graph model for link prediction of novel phosphorylated substrates of kinases. PeerJ, 2023; 11:e16164; doi: 10.7717/peerj.16164
4.
AndersenSD, KeijzersG, RampakakisE, et al.14-3-3 Checkpoint regulatory proteins interact specifically with DNA repair protein Human Exonuclease 1 (hEXO1) via a semi-conserved motif. DNA Repair (Amst), 2012; 11(3):267–277; doi: 10.1016/j.dnarep.2011.11.007
5.
AwwadSW, Abu-ZhayiaER, Guttmann-RavivN, et al.NELF-E is recruited to DNA double-strand break sites to promote transcriptional repression and repair. EMBO Rep, 2017; 18(5):745–764; doi: 10.15252/embr.201643191
BaiE, DongM, LinX, et al.Expressional and functional characteristics of checkpoint kinase 1 as a prognostic biomarker in hepatocellular carcinoma. Transl Cancer Res, 2022; 11(12):4272–4288; doi: 10.21037/tcr-22-1701
8.
BaillieKE, StirlingPC. Beyond kinases: Targeting replication stress proteins in cancer therapy. Trends Cancer, 2021; 7(5):430–446; doi: 10.1016/j.trecan.2020.10.010
9.
BaoJ, YuY, ChenJ, et al.MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway. Cell Death Dis, 2018; 9(10):1045; doi: 10.1038/s41419-018-1020-0
10.
Bargiela-IparraguirreJ, Prado-MarchalL, Fernandez-FuenteM, et al.CHK1 expression in gastric cancer is modulated by p53 and RB1/E2F1: Implications in Chemo/radiotherapy response. Sci Rep, 2016; 6:21519; doi: 10.1038/srep21519
BartucciM, SvenssonS, RomaniaP, et al.Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy. Cell Death Differ, 2012; 19(5):768–778; doi: 10.1038/cdd.2011.170
13.
BecktaJM, DeverSM, GnawaliN, et al.Mutation of the BRCA1 SQ-cluster results in aberrant mitosis, reduced homologous recombination, and a compensatory increase in non-homologous end joining. Oncotarget, 2015; 6(29):27674–27687; doi: 10.18632/oncotarget.4876
14.
BlasiusM, FormentJV, ThakkarN, et al.A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1. Genome Biol, 2011; 12(8):R78; doi: 10.1186/gb-2011-12-8-r78
15.
Carreras PuigvertJ, von StechowL, SiddappaR, et al.Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells. Sci Signal, 2013; 6(259):ra5; doi: 10.1126/scisignal.2003208
16.
CarteeGD. Roles of TBC1D1 and TBC1D4 in insulin- and exercise-stimulated glucose transport of skeletal muscle. Diabetologia, 2015; 58(1):19–30; doi: 10.1007/s00125-014-3395-5
17.
ChakravartyD, GaoJ, PhillipsSM, et al.OncoKB: A precision oncology knowledge base. JCO Precis Oncol, 2017; 2017:PO.17.00011; doi: 10.1200/PO.17.00011
18.
ChanL-K, HoDW-H, KamCS, et al.RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma. J Hepatol, 2021; 74(2):360–371; doi: 10.1016/j.jhep.2020.08.036
19.
ChenP, LuoC, DengY, et al.The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: Implications for Chk1 regulation. Cell, 2000; 100(6):681–692; doi: 10.1016/s0092-8674(00)80704-7
20.
CiciròY, RagusaD, SalaA. Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies. Sci Rep, 2024; 14(1):4461; doi: 10.1038/s41598-024-55080-y
21.
CybulskiC, ZamaniN, KluźniakW, et al.Variants in ATRIP are associated with breast cancer susceptibility in the polish population and UK Biobank. Am J Hum Genet, 2023; 110(4):648–662; doi: 10.1016/j.ajhg.2023.03.002
22.
de BoerHR, Guerrero LlobetS, van VugtMATM. Controlling the response to DNA damage by the APC/C-Cdh1. Cell Mol Life Sci, 2016; 73(5):949–960; doi: 10.1007/s00018-015-2096-7
23.
DorardC, MadryC, BuhardO, et al.RAF1 contributes to cell proliferation and STAT3 activation in colorectal cancer independently of microsatellite and KRAS status. Oncogene, 2023; 42(20):1649–1660; doi: 10.1038/s41388-023-02683-w
24.
DoughertyMK, MüllerJ, RittDA, et al.Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell, 2005; 17(2):215–224; doi: 10.1016/j.molcel.2004.11.055
25.
DumbauldDW, MichaelKE, HanksSK, et al.Focal adhesion kinase-dependent regulation of adhesive forces involves vinculin recruitment to focal adhesions. Biol Cell, 2010; 102(4):203–213; doi: 10.1042/BC20090104
26.
EmptageRP, SchoenbergerMJ, FergusonKM, et al.Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain. J Biol Chem, 2017; 292(46):19024–19033; doi: 10.1074/jbc.M117.811265
27.
EngelU, ZhanY, LongJB, et al.Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin. Cytoskeleton (Hoboken), 2014; 71(3):195–209; doi: 10.1002/cm.21164
28.
EspositoF, GiuffridaR, RacitiG, et al.Wee1 kinase: A potential target to overcome tumor resistance to therapy. Int J Mol Sci, 2021; 22(19):10689; doi: 10.3390/ijms221910689
29.
FeijooC, Hall-JacksonC, WuR, et al.Activation of mammalian Chk1 during DNA replication arrest: A role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol, 2001; 154(5):913–923; doi: 10.1083/jcb.200104099
30.
FlaggsG, PlugAW, DunksKM, et al.Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes. Curr Biol, 1997; 7(12):977–986; doi: 10.1016/s0960-9822(06)00417-9
31.
FogartyP, CampbellSD, Abu-ShumaysR, et al.The drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity. Curr Biol, 1997; 7(6):418–426; doi: 10.1016/s0960-9822(06)00189-8
32.
GateiM, SloperK, SorensenC, et al.Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem, 2003; 278(17):14806–14811; doi: 10.1074/jbc.M210862200
33.
Giridhara PremaS, ChandrasekaranJ, KanekarS, et al.Cisplatin and procaterol combination in gastric cancer? Targeting checkpoint kinase 1 for cancer drug discovery and repurposing by an integrated computational and experimental approach. OMICS, 2024; 28(1):8–23; doi: 10.1089/omi.2023.0163
34.
GoelR, HarshaHC, PandeyA, et al.Human protein reference database and human proteinpedia as resources for phosphoproteome analysis. Mol Biosyst, 2012; 8(2):453–463; doi: 10.1039/c1mb05340j
35.
GopalakrishnanAP, ShivamurthyPB, AhmedM, et al.Positional distribution and conservation of major phosphorylated sites in the human kinome. Front Mol Biosci, 2025; 12:1557835; doi: 10.3389/fmolb.2025.1557835
36.
HeffernanTP, SimpsonDA, FrankAR, et al.An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage. Mol Cell Biol, 2002; 22(24):8552–8561; doi: 10.1128/MCB.22.24.8552-8561.2002
37.
HerJ, RayC, AltshulerJ, et al.53BP1 mediates ATR-Chk1 signaling and protects replication forks under conditions of replication stress. Mol Cell Biol, 2018; 38(8):e00472–e00417; doi: 10.1128/MCB.00472-17
38.
HirokawaT, ShiotaniB, ShimadaM, et al.CBP-93872 inhibits NBS1-mediated ATR activation, abrogating maintenance of the DNA double-strand break-specific G2 checkpoint. Cancer Res, 2014; 74(14):3880–3889; doi: 10.1158/0008-5472.CAN-13-3604
39.
HongJ, HuK, YuanY, et al.CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma. J Clin Invest, 2012; 122(6):2165–2175; doi: 10.1172/JCI61380
40.
HornbeckPV, ZhangB, MurrayB, et al.PhosphoSitePlus, 2014: Mutations, PTMs and recalibrations. Nucleic Acids Res, 2015; 43(Database issue):D512–D20; doi: 10.1093/nar/gku1267
41.
HromasR, WilliamsonEA, FnuS, et al.Chk1 phosphorylation of metnase enhances DNA repair but inhibits replication fork restart. Oncogene, 2012; 31(38):4245–4254; doi: 10.1038/onc.2011.586
42.
HuC, XieJ, FeiX, et al.Overexpressed RPS6KA1 and its potential diagnostic value in head and neck squamous cell carcinoma. Discov Oncol, 2025; 16(1):60; doi: 10.1007/s12672-025-01799-7
43.
HuangK-Y, WuH-Y, ChenY-J, et al.RegPhos 2.0: An updated resource to explore protein kinase-substrate phosphorylation networks in mammals. Database (Oxford), 2014; 2014(0):bau034; doi: 10.1093/database/bau034
44.
IijimaK, MuranakaC, KobayashiJ, et al.NBS1 regulates a novel apoptotic pathway through Bax activation. DNA Repair (Amst), 2008; 7(10):1705–1716; doi: 10.1016/j.dnarep.2008.06.013
45.
InoueY, KitagawaM, TayaY. Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA Damage. EMBO J, 2007; 26(8):2083–2093; doi: 10.1038/sj.emboj.7601652
46.
IsobeS-Y, NagaoK, NozakiN, et al.Inhibition of RIF1 by SCAI allows BRCA1-mediated repair. Cell Rep, 2017; 20(2):297–307; doi: 10.1016/j.celrep.2017.06.056
47.
JiangY, DongY, LuoY, et al.AMPK-mediated phosphorylation on 53BP1 promotes c-NHEJ. Cell Rep, 2021; 34(7):108713; doi: 10.1016/j.celrep.2021.108713
48.
JohnL, GeorgeM, DcunhaL, et al.Elucidating the phosphoregulatory network of predominant phosphosite in AXL kinase: An integrative bioinformatic approach. J Proteins Proteom, 2024; 15(3):429–447; doi: 10.1007/s42485-024-00147-7
49.
JohnsonJL, YaronTM, HuntsmanEM, et al.An atlas of substrate specificities for the human serine/threonine kinome. Nature, 2023; 613(7945):759–766; doi: 10.1038/s41586-022-05575-3
50.
KamburovA, HerwigR. ConsensusPathDB 2022: Molecular interactions update as a resource for network biology. Nucleic Acids Res, 2022; 50(D1):D587–D595; doi: 10.1093/nar/gkab1128
51.
KasaharaK, GotoH, EnomotoM, et al.14-3-3gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. Embo J, 2010; 29(16):2802–2812; doi: 10.1038/emboj.2010.157
52.
KciukM, GruszkaR, AleksandrowiczM, et al.ATR-CHK1 axis inhibitors in gastric cancer treatment. Int J Mol Sci, 2025; 26(16):7709; doi: 10.3390/ijms26167709
53.
KingFW, SkeenJ, HayN, et al.Inhibition of Chk1 by Activated PKB/Akt. Cell Cycle, 2004; 3(5):634–637.
54.
KnijnenburgTA, WangL, ZimmermannMT, et al.; Cancer Genome Atlas Research Network. Genomic and molecular landscape of DNA damage repair deficiency across the cancer genome atlas. Cell Rep, 2018; 23(1):239–254.e6; doi: 10.1016/j.celrep.2018.03.076
55.
KrugK, MertinsP, ZhangB, et al.A curated resource for phosphosite-specific signature analysis. Mol Cell Proteomics, 2019; 18(3):576–593; doi: 10.1074/mcp.TIR118.000943
56.
LamMH, LiuQ, ElledgeSJ, et al.Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell, 2004; 6(1):45–59; doi: 10.1016/j.ccr.2004.06.015
57.
LeeJ-H, ChoyML, NgoL, et al.Role of Checkpoint Kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors. Proc Natl Acad Sci U S A, 2011; 108(49):19629–19634; doi: 10.1073/pnas.1117544108
58.
LiP, GotoH, KasaharaK, et al.P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation. Mol Biol Cell, 2012; 23(8):1582–1592; doi: 10.1091/mbc.E11-10-0883
59.
LiangZ, LiuT, LiQ, et al.Deciphering the functional landscape of phosphosites with deep neural network. Cell Rep, 2023; 42(9):113048; doi: 10.1016/j.celrep.2023.113048
60.
LindingR, JensenLJ, PasculescuA, et al.NetworKIN: A resource for exploring cellular phosphorylation networks. Nucleic Acids Res, 2008; 36(Database issue):D695–D699; doi: 10.1093/nar/gkm902
61.
LiuQ, PalomeroL, MooreJ, et al.Loss of TGFβ signaling increases alternative end-joining DNA repair that sensitizes to genotoxic therapies across cancer types. Sci Transl Med, 2021; 13(580):eabc4465; doi: 10.1126/scitranslmed.abc4465
62.
LiuQ, TurnerKM, Alfred YungWK, et al.Role of AKT signaling in DNA repair and clinical response to cancer therapy. Neuro Oncol, 2014; 16(10):1313–1323; doi: 10.1093/neuonc/nou058
63.
LubabaF, GeorgeM, AhmedM, et al.Theranostic target NSUN2, a C(5)-methyltransferase, phospho-regulatory network uncovered with systematic assembly of 805 datasets. OMICS, 2025; 29(4):164–177; doi: 10.1089/omi.2025.0025
64.
LundgrenK, HolmK, NordenskjöldB, et al.Gene products of chromosome 11q and their association with CCND1 gene amplification and tamoxifen resistance in premenopausal breast cancer. Breast Cancer Res, 2008; 10(5):R81; doi: 10.1186/bcr2150
65.
LussanaA, Müller-DottS, Saez-RodriguezJ, et al.PhosX: Data-driven kinase activity inference from phosphoproteomics experiments. Bioinformatics, 2024; 40(12):btae697; doi: 10.1093/bioinformatics/btae697
66.
MahinA, GopalakrishnanAP, AhmedM, et al.Orchestrating intracellular calcium signaling cascades by phosphosite-centric regulatory network: A Comprehensive Analysis on Kinases CAMKK1 and CAMKK2. OMICS, 2025; 29(4):139–153; doi: 10.1089/omi.2024.0196
MatthewsLA, GuarnéA. Dbf4: The whole is greater than the sum of its parts. Cell Cycle, 2013; 12(8):1180–1188; doi: 10.4161/cc.24416
69.
MeiL, ZhangJ, HeK, et al.Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: Where we stand. J Hematol Oncol, 2019; 12(1):43; doi: 10.1186/s13045-019-0733-6
70.
MeiY, LiuY-B, CaoS, et al.RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein phosphatase 1-mediated activation of Wnt/β-catenin signaling. Cell Death Dis, 2018; 9(10):942; doi: 10.1038/s41419-018-0972-4
71.
MijnesJ, VeeckJ, GaisaNT, et al.Promoter methylation of DNA Damage Repair (DDR) genes in human tumor entities:/is almost exclusively methylated in bladder cancer. Clin Epigenetics, 2018; 10:15; doi: 10.1186/s13148-018-0447-6
72.
MyersJS, ZhaoR, XuX, et al.Cyclin-dependent kinase 2 dependent phosphorylation of ATRIP regulates the G2-M checkpoint response to DNA damage. Cancer Res, 2007; 67(14):6685–6690; doi: 10.1158/0008-5472.CAN-07-0495
73.
NguyenCL, PossematoR, BauerleinEL, et al.Nek4 regulates entry into replicative senescence and the response to DNA damage in human fibroblasts. Mol Cell Biol, 2012; 32(19):3963–3977; doi: 10.1128/MCB.00436-12
74.
OkitaN, MinatoS, OhmiE, et al.DNA damage-induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism. FEBS Lett, 2012; 586(22):3974–3979; doi: 10.1016/j.febslet.2012.09.048
75.
OttoT, SicinskiP. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer, 2017; 17(2):93–115; doi: 10.1038/nrc.2016.138
OughtredR, RustJ, ChangC, et al.The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions. Protein Sci, 2021; 30(1):187–200; doi: 10.1002/pro.3978
78.
ParcaL, ArianoB, CabibboA, et al.Kinome-wide identification of phosphorylation networks in eukaryotic proteomes. Bioinformatics, 2019; 35(3):372–379; doi: 10.1093/bioinformatics/bty545
79.
Parrilla-CastellarER, ArlanderSJH, KarnitzL. Dial 9-1-1 for DNA damage: The Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA Repair (Amst), 2004; 3(8–9):1009–1014; doi: 10.1016/j.dnarep.2004.03.032
80.
PatilM, PablaN, DongZ. Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci, 2013; 70(21):4009–4021; doi: 10.1007/s00018-013-1307-3
81.
PichierriP, RosselliF. The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. Embo J, 2004; 23(5):1178–1187; doi: 10.1038/sj.emboj.7600113
82.
PomellaS, CassandriM, MelaiuO, et al.DNA damage response gene signature as potential treatment markers for oral squamous cell carcinoma. Int J Mol Sci, 2023; 24(3):2673; doi: 10.3390/ijms24032673
83.
PriyankaP, GopalakrishnanAP, NisarM, et al.A global phosphosite-correlated network map of Thousand and One Kinase 1 (TAOK1). Int J Biochem Cell Biol, 2024; 170:106558; doi: 10.1016/j.biocel.2024.106558
84.
QiH, KikuchiM, YoshinoY, et al.BRCA1 transports the DNA damage signal for CDDP-induced centrosome amplification through the centrosomal aurora A. Cancer Sci, 2022; 113(12):4230–4243; doi: 10.1111/cas.15573
85.
RaiA, YelamanchiSD, RadotraBD, et al.Phosphorylation of β-catenin at serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours. Acta Neuropathol Commun, 2022; 10(1):138; doi: 10.1186/s40478-022-01441-5
86.
Ray-DavidH, RomeoY, LavoieG, et al.RSK promotes G2 DNA damage checkpoint silencing and participates in melanoma chemoresistance. Oncogene, 2013; 32(38):4480–4489; doi: 10.1038/onc.2012.472
87.
SanchezY, WongC, ThomaRS, et al.Conservation of the Chk1 checkpoint pathway in mammals: Linkage of DNA damage to Cdk regulation through Cdc25. Science, 1997; 277(5331):1497–1501; doi: 10.1126/science.277.5331.1497
88.
SanjeevD, GeorgeM, JohnL, et al.Tyr352 as a predominant phosphosite in the understudied kinase and molecular target, HIPK1: Implications for cancer therapy. OMICS, 2024a;28(3):111–124; doi: 10.1089/omi.2023.0244
89.
SanjeevD, MendonS, GeorgeM, et al.Exploring the phospho-landscape of NEK6 kinase: Systematic annotation of phosphosites and their implications as biomarkers in carcinogenesis. J Proteins Proteom, 2024b;15(3):377–393; doi: 10.1007/s42485-024-00146-8
90.
Segal-RazH, MassG, Baranes-BacharK, et al.ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair. EMBO Rep, 2011; 12(7):713–719; doi: 10.1038/embor.2011.96
91.
ShimuraY, KurodaJ, RiM, et al.RSK2(Ser227) at N-Terminal kinase domain is a potential therapeutic target for multiple myeloma. Mol Cancer Ther, 2012; 11(12):2600–2609; doi: 10.1158/1535-7163.MCT-12-0605
92.
SongJ, MaJ, LiuX, et al.The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway. NPJ Regen Med, 2023; 8(1):20; doi: 10.1038/s41536-023-00294-3
93.
SriaishwaryaS, LakshmiBS. RAD23B mediated proteasomal degradation occurs through p38 MAPK/ATF-2/RAD23B axis under nutrient-deprived conditions in breast cancer. Cell Biol Int, 2024:973–983; doi: 10.1002/cbin.12160
94.
SunL, LiuX, SongSet al.Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer. Open Med (Wars), 2021; 16(1):1705–1717; doi: 10.1515/med-2021-0388, 34825062
95.
TaylorMRG, YeelesJTP. The initial response of a eukaryotic replisome to DNA damage. Mol Cell, 2018; 70(6):1067–1080.e12; doi: 10.1016/j.molcel.2018.04.022
96.
TsitsiridisG, SteinkampR, GiurgiuM, et al.CORUM: The comprehensive resource of mammalian protein complexes-2022. Nucleic Acids Res, 2023; 51(D1):D539–D545; doi: 10.1093/nar/gkac1015
97.
UniProt Consortium. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res, 2023; 51(D1):D523–D531; doi: 10.1093/nar/gkac1052
98.
WalkerM, BlackEJ, OehlerV, et al.Chk1 C-terminal regulatory phosphorylation mediates checkpoint activation by de-repression of Chk1 catalytic activity. Oncogene, 2009; 28(24):2314–2323; doi: 10.1038/onc.2009.102
99.
WalworthN, DaveyS, BeachD. Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2. Nature, 1993; 363(6427):368–371; doi: 10.1038/363368a0
100.
WangJ, HanX, FengX, et al.Coupling cellular localization and function of Checkpoint Kinase 1 (Chk1) in checkpoints and cell viability. J Biol Chem, 2012; 287(30):25501–25509; doi: 10.1074/jbc.M112.350397
101.
WilliamsonEA, WuY, SinghS, et al.The DNA repair component Metnase regulates Chk1 stability. Cell Div, 2014; 9:1; doi: 10.1186/1747-1028-9-1
102.
WilskerD, PetermannE, HelledayT, et al.Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control. Proc Natl Acad Sci U S A, 2008; 105(52):20752–20757; doi: 10.1073/pnas.0806917106
103.
WoodRD, MitchellM, LindahlT. Human DNA repair genes, 2005. Mutat Res, 2005; 577(1–2):275–283; doi: 10.1016/j.mrfmmm.2005.03.007
104.
WuM, PangJ-S, SunQ, et al.The clinical significance of CHEK1 in breast cancer: A high-throughput data analysis and immunohistochemical study. Int J Clin Exp Pathol, 2019; 12(1):1–20.
105.
YangC, WangH, XuY, et al.The kinetochore protein Bub1 participates in the DNA damage response. DNA Repair (Amst), 2012; 11(2):185–191; doi: 10.1016/j.dnarep.2011.10.018
106.
YinC, SunY, LiH, et al.MiR-424-5p suppresses tumor growth and progression by directly targeting CHEK1 and activating cell cycle pathway in hepatocellular carcinoma. Heliyon, 2024; 10(18):e37769; doi: 10.1016/j.heliyon.2024.e37769
107.
ZhangY, SongC, WangL, et al.Zombies never die: The double life Bub1 lives in mitosis. Front Cell Dev Biol, 2022; 10:870745; doi: 10.3389/fcell.2022.870745
108.
ZhaoH, WatkinsJL, Piwnica-WormsH. Disruption of the checkpoint Kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A, 2002; 99(23):14795–14800; doi: 10.1073/pnas.182557299
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
