DNA damage response (WP707)

Homo sapiens

This is the first pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and ATR) which are connected to the sources of DNA damage (in blue). The two central genes can be divides furthermore into their most important genes. In the ATM pathway are the most important genes TP53 and CHEK2 and on the other hand in the ATR pathway is this CHEK1. If it is not mentioned different, the processes take place in the cell cytoplasm. The goal of this first pathway is to give an overview of the most important gene products, processes and changes in the cell condition through the DNA damage response pathway and at the same time to keep it clearly arranged. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP707 CPTAC Assay Portal]


Jonas Hummel , Alex Pico , Stan Gaj , Martina Summer-Kutmon , Martijn Van Iersel , Christine Chichester , Daniela Digles , Kristina Hanspers , Zahra Roudbari , Egon Willighagen , Ryan Miller , Finterly Hu , Eric Weitz , and Vanessa Sousa


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Homo sapiens


CPTAC PancCanNet


Pathway Ontology

DNA damage response pathway p53 signaling pathway stress response pathway


Label Type Compact URI Comment
Caffeine Metabolite chemspider:2424
7-hydroxystaurosporine Metabolite chemspider:65225
Estradiol Metabolite chebi:16469
Alkylating agents Metabolite chebi:22333
RB1 GeneProduct ensembl:ENSG00000139687
AKT1 GeneProduct ensembl:ENSG00000142208
CDC25C GeneProduct ensembl:ENSG00000158402
CASP8 GeneProduct ensembl:ENSG00000064012
HUS1 GeneProduct ensembl:ENSG00000188996
CCNB1 GeneProduct ensembl:ENSG00000134057
MRE11 GeneProduct ncbigene:4361
CHEK1 GeneProduct ensembl:ENSG00000149554
ATR GeneProduct ensembl:ENSG00000175054
CDKN1A GeneProduct ensembl:ENSG00000124762
RAD52 GeneProduct ensembl:ENSG00000002016
c-Myc GeneProduct ncbigene:4609
CASP3 GeneProduct ensembl:ENSG00000164305
MDM2 GeneProduct ensembl:ENSG00000135679
CDK6 GeneProduct ensembl:ENSG00000105810
DDB2 GeneProduct ensembl:ENSG00000134574
PML GeneProduct ensembl:ENSG00000140464
CCND3 GeneProduct ensembl:ENSG00000112576
BID GeneProduct ensembl:ENSG00000015475
TP53AIP1 GeneProduct ensembl:ENSG00000120471
H2AFX GeneProduct ensembl:ENSG00000188486
RAD1 GeneProduct ensembl:ENSG00000113456
FANCD2 GeneProduct ensembl:ENSG00000144554
GADD45A GeneProduct ensembl:ENSG00000116717
FAS GeneProduct ensembl:ENSG00000026103
PIDD GeneProduct ncbigene:55367
CCND1 GeneProduct ensembl:ENSG00000110092
RAD9A GeneProduct ensembl:ENSG00000172613
CYCS GeneProduct ensembl:ENSG00000172115
CDC2 GeneProduct ensembl:ENSG00000170312
GADD45B GeneProduct ensembl:ENSG00000099860
RB1 GeneProduct ensembl:ENSG00000139687
CDK5 GeneProduct ensembl:ENSG00000164885
PMAIP1 GeneProduct ensembl:ENSG00000141682
CCNB3 GeneProduct ensembl:ENSG00000147082
SESN1 GeneProduct ensembl:ENSG00000080546
RAD51 GeneProduct ensembl:ENSG00000051180
RRM2B GeneProduct ensembl:ENSG00000048392
CDKN1B GeneProduct ensembl:ENSG00000111276
CDK2 GeneProduct ensembl:ENSG00000123374
GADD45G GeneProduct ensembl:ENSG00000130222
SFN GeneProduct ensembl:ENSG00000175793
ATRIP GeneProduct ncbigene:84126
BBC3 GeneProduct ensembl:ENSG00000105327
RPA2 GeneProduct ensembl:ENSG00000117748
RAD50 GeneProduct ensembl:ENSG00000113522
TP53 GeneProduct ensembl:ENSG00000141510
TLK1 GeneProduct ensembl:ENSG00000198586
CDK4 GeneProduct ensembl:ENSG00000135446
CCNE1 GeneProduct ensembl:ENSG00000105173
TNFRSF10B GeneProduct ensembl:ENSG00000120889
GADD45G GeneProduct ensembl:ENSG00000130222
BAX GeneProduct ensembl:ENSG00000087088
RAD17 GeneProduct ensembl:ENSG00000152942
BRCA1 GeneProduct ensembl:ENSG00000012048
CHEK2 GeneProduct ensembl:ENSG00000183765
SMC1A GeneProduct ensembl:ENSG00000072501
CREB GeneProduct ncbigene:1385
ABL1 GeneProduct ensembl:ENSG00000097007
E2F1 GeneProduct ensembl:ENSG00000101412
PRKDC GeneProduct ensembl:ENSG00000253729
APAF1 GeneProduct ensembl:ENSG00000120868
CASP9 GeneProduct ensembl:ENSG00000132906
CCNB2 GeneProduct ensembl:ENSG00000157456
E2F1 GeneProduct ensembl:ENSG00000101412
TLK2 GeneProduct ensembl:ENSG00000146872
CDC25A GeneProduct ensembl:ENSG00000164045
NBN GeneProduct ncbigene:4683
GADD45B GeneProduct ensembl:ENSG00000099860
CCNE2 GeneProduct ensembl:ENSG00000175305
CCND2 GeneProduct ensembl:ENSG00000118971
GADD45A GeneProduct ensembl:ENSG00000116717
ATM GeneProduct ensembl:ENSG00000149311
RFC GeneProduct ncbigene:5981


  1. The Bcl-2 family: roles in cell survival and oncogenesis. Cory S, Huang DCS, Adams JM. Oncogene. 2003 Nov 24;22(53):8590–607. PubMed Europe PMC Scholia
  2. Dynamics of the p53-Mdm2 feedback loop in individual cells. Lahav G, Rosenfeld N, Sigal A, Geva-Zatorsky N, Levine AJ, Elowitz MB, et al. Nat Genet. 2004 Feb;36(2):147–50. PubMed Europe PMC Scholia
  3. Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Zhou BBS, Bartek J. Nat Rev Cancer. 2004 Mar;4(3):216–25. PubMed Europe PMC Scholia
  4. Wagging the dogma; tissue-specific cell cycle control in the mouse embryo. Pagano M, Jackson PK. Cell. 2004 Sep 3;118(5):535–8. PubMed Europe PMC Scholia
  5. Transcription - guarding the genome by sensing DNA damage. Ljungman M, Lane DP. Nat Rev Cancer. 2004 Sep;4(9):727–37. PubMed Europe PMC Scholia
  6. Living with or without cyclins and cyclin-dependent kinases. Sherr CJ, Roberts JM. Genes Dev. 2004 Nov 15;18(22):2699–711. PubMed Europe PMC Scholia
  7. Chromosomal instability in oral cancer cells. Reshmi SC, Gollin SM. J Dent Res. 2005 Feb;84(2):107–17. PubMed Europe PMC Scholia
  8. p53: traffic cop at the crossroads of DNA repair and recombination. Sengupta S, Harris CC. Nat Rev Mol Cell Biol. 2005 Jan;6(1):44–55. PubMed Europe PMC Scholia
  9. The role of BH3-only proteins in the immune system. Strasser A. Nat Rev Immunol. 2005 Mar;5(3):189–200. PubMed Europe PMC Scholia
  10. Surviving the breakup: the DNA damage checkpoint. Harrison JC, Haber JE. Annu Rev Genet. 2006;40:209–35. PubMed Europe PMC Scholia
  11. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Gil J, Peters G. Nat Rev Mol Cell Biol. 2006 Sep;7(9):667–77. PubMed Europe PMC Scholia
  12. Polycomb silencers control cell fate, development and cancer. Sparmann A, van Lohuizen M. Nat Rev Cancer. 2006 Nov;6(11):846–56. PubMed Europe PMC Scholia
  13. Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Toledo F, Wahl GM. Nat Rev Cancer. 2006 Dec;6(12):909–23. PubMed Europe PMC Scholia
  14. p53 in health and disease. Vousden KH, Lane DP. Nat Rev Mol Cell Biol. 2007 Apr;8(4):275–83. PubMed Europe PMC Scholia
  15. CDC25 phosphatases in cancer cells: key players? Good targets? Boutros R, Lobjois V, Ducommun B. Nat Rev Cancer. 2007 Jul;7(7):495–507. PubMed Europe PMC Scholia
  16. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Wang W. Nat Rev Genet. 2007 Oct;8(10):735–48. PubMed Europe PMC Scholia
  17. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Löbrich M, Jeggo PA. Nat Rev Cancer. 2007 Nov;7(11):861–9. PubMed Europe PMC Scholia
  18. CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin? Antoni L, Sodha N, Collins I, Garrett MD. Nat Rev Cancer. 2007 Dec;7(12):925–36. PubMed Europe PMC Scholia
  19. Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale? Chargari C, Toillon RA, Macdermed D, Castadot P, Magné N. Lancet Oncol. 2009 Jan;10(1):53–60. PubMed Europe PMC Scholia
  20. p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage. Gong H, Cao Y, Han G, Zhang Y, You Q, Wang Y, et al. Int J Oncol. 2017 May;50(5):1785–91. PubMed Europe PMC Scholia