DNA Damage Response (Homo sapiens)

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152, 7, 10, 13, 14165, 6516151, 3, 4, 9, 11...161, 3, 4, 9, 11...85, 6151, 3, 4, 9, 11...5, 617161716516816816161619176171655, 61, 3, 4, 9, 11...1, 3, 4, 9, 11...1, 3, 4, 9, 11...5, 616161, 3, 4, 9, 11...Specialized:Somatic hypermutaionV(D)J recombinationClass switchingCellDNA repair and damage preventionDouble-strand breaksG2–MCheckpointBulky DNA lesionGene productAlkylating agentsG2/M transitionMetaboliteBlocked replicationDNA repairBlocked transcriptionReplication stressChromatinremodellingExtral cellularSpaceCaption:G2/M checkpointDNA adductCell survivalROSDifferent pathwayDNA damage ATM dependentExogenous:Cigarette SmokeCaffeineRadiation (UV)ClastogenesHypoxiaGenotoxic drugsChange in the Cell conditionInhibitionActivationmitoch-ondrionChromatin alterationDNA damage sourceMembraneG1/S transitionROSCell-cycle progressionEndogenous:Collapsed replication forksSingle stranded DNA replication breaksFree radicals (ROS)CDK6RFCApoptosisCDKN1BCYCSCHEK2CCNE1CDK4GADD45ACell CycleCASP9BIDRAD50GADD45GE2F1CREBSFNATRIPGADD45BBRCA1BBC3FANCD2H2AFXRB1SMC1ARAD17CHEK1SenescenceCCND1CDC2ATMRAD52MDM2RPA2GADD45BCDC25APIDDNBNATRBAXCCND2CCNB1CCNB3CDC25CCCNB2TP53E2F1GADD45ACaffeinePMLRAD51GADD45GRAD9ASESN1ABL1CDK2CASP3CCNE27-hydroxystaurosporineCASP8DDB2TLK2APAF1FASEstradiolTNFRSF10BMRE11c-MycPRKDCTP53AIP1CCND3RB1CDK5RAD1HUS1CDKN1APMAIP1TLK1RRM2B


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

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Ontology Terms



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  1. Lahav G, Rosenfeld N, Sigal A, Geva-Zatorsky N, Levine AJ, Elowitz MB, Alon U; ''Dynamics of the p53-Mdm2 feedback loop in individual cells.''; Nat Genet, 2004 PubMed
  2. Strasser A; ''The role of BH3-only proteins in the immune system.''; Nat Rev Immunol, 2005 PubMed
  3. Toledo F, Wahl GM; ''Regulating the p53 pathway: in vitro hypotheses, in vivo veritas.''; Nat Rev Cancer, 2006 PubMed
  4. Sherr CJ, Roberts JM; ''Living with or without cyclins and cyclin-dependent kinases.''; Genes Dev, 2004 PubMed
  5. Cory S, Huang DC, Adams JM; ''The Bcl-2 family: roles in cell survival and oncogenesis.''; Oncogene, 2003 PubMed
  6. Vousden KH, Lane DP; ''p53 in health and disease.''; Nat Rev Mol Cell Biol, 2007 PubMed
  7. Antoni L, Sodha N, Collins I, Garrett MD; ''CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?''; Nat Rev Cancer, 2007 PubMed
  8. Löbrich M, Jeggo PA; ''The impact of a negligent G2/M checkpoint on genomic instability and cancer induction.''; Nat Rev Cancer, 2007 PubMed
  9. Sparmann A, van Lohuizen M; ''Polycomb silencers control cell fate, development and cancer.''; Nat Rev Cancer, 2006 PubMed
  10. Boutros R, Lobjois V, Ducommun B; ''CDC25 phosphatases in cancer cells: key players? Good targets?''; Nat Rev Cancer, 2007 PubMed
  11. Zhou BB, Bartek J; ''Targeting the checkpoint kinases: chemosensitization versus chemoprotection.''; Nat Rev Cancer, 2004 PubMed
  12. Gil J, Peters G; ''Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all.''; Nat Rev Mol Cell Biol, 2006 PubMed
  13. Reshmi SC, Gollin SM; ''Chromosomal instability in oral cancer cells.''; J Dent Res, 2005 PubMed
  14. Sengupta S, Harris CC; ''p53: traffic cop at the crossroads of DNA repair and recombination.''; Nat Rev Mol Cell Biol, 2005 PubMed
  15. Chargari C, Toillon RA, Macdermed D, Castadot P, Magné N; ''Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale?''; Lancet Oncol, 2009 PubMed
  16. Wang W; ''Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins.''; Nat Rev Genet, 2007 PubMed
  17. Harrison JC, Haber JE; ''Surviving the breakup: the DNA damage checkpoint.''; Annu Rev Genet, 2006 PubMed
  18. Pagano M, Jackson PK; ''Wagging the dogma; tissue-specific cell cycle control in the mouse embryo.''; Cell, 2004 PubMed
  19. Ljungman M, Lane DP; ''Transcription - guarding the genome by sensing DNA damage.''; Nat Rev Cancer, 2004 PubMed


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94731view14:50, 5 October 2017Ryanmillerconnected lines
82937view22:59, 13 November 2015AlexanderPicofixed character corruption
82193view16:31, 12 September 2015EgonwFixed weird characters in autors names.
82188view17:24, 11 September 2015EgonwMarked 'Alkylating agents' as a metabolite (to make the ChEBI link out work).
81804view14:56, 30 August 2015EgonwGave 'alkylating agents' a ChEBI identifier.
79975view12:15, 29 April 2015ZariCorrected I Ensembl
78527view10:29, 7 January 2015MaintBotadded missing graphIds
75226view18:29, 12 May 2014Khanspersimproved layout, fixed legend
70110view19:07, 12 July 2013MaintBotupdated to 2013 schema
69905view19:30, 11 July 2013AlexanderPicoModified title
67787view15:18, 26 June 2013DdiglesOntology Term : 'DNA damage response pathway' added !
67155view10:13, 26 June 2013Christine ChichesterOntology Term : 'stress response pathway' added !
59084view22:02, 21 February 2013MaintBotUpdated Ensembl data source
45196view10:06, 7 October 2011MartijnVanIerselOntology Term : 'p53 signaling pathway' added !
41047view23:16, 1 March 2011MaintBotRemoved redundant pathway information and comments
38647view12:30, 23 September 2010Mkutmonadding pathway links for "cell cycle", "apoptosis" and "senescence"
38431view07:48, 13 September 2010Stan.gajMDM2 - Literature added
38403view16:35, 9 September 2010Stan.gajAdded MDM2 regulation of TP53
34441view18:18, 10 December 2009MaintBotAutomatic update of empty xrefs
33418view14:52, 30 November 2009MaintBotRemoved group label
30259view04:49, 25 July 2009AlexanderPicoModified categories
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External references


View all...
NameTypeDatabase referenceComment
7-hydroxystaurosporineMetabolite65225 (Chemspider)
ABL1GeneProductENSG00000097007 (Ensembl)
APAF1GeneProductENSG00000120868 (Ensembl)
ATMGeneProductENSG00000149311 (Ensembl)
ATRGeneProductENSG00000175054 (Ensembl)
ATRIPGeneProduct84126 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
BAXGeneProductENSG00000087088 (Ensembl)
BBC3GeneProductENSG00000105327 (Ensembl)
BIDGeneProductENSG00000015475 (Ensembl)
BRCA1GeneProductENSG00000012048 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CCNB1GeneProductENSG00000134057 (Ensembl)
CCNB2GeneProductENSG00000157456 (Ensembl)
CCNB3GeneProductENSG00000147082 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CCND2GeneProductENSG00000118971 (Ensembl)
CCND3GeneProductENSG00000112576 (Ensembl)
CCNE1GeneProductENSG00000105173 (Ensembl)
CCNE2GeneProductENSG00000175305 (Ensembl)
CDC25AGeneProductENSG00000164045 (Ensembl)
CDC25CGeneProductENSG00000158402 (Ensembl)
CDC2GeneProductENSG00000170312 (Ensembl)
CDK2GeneProductENSG00000123374 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDK5GeneProductENSG00000164885 (Ensembl)
CDK6GeneProductENSG00000105810 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CDKN1BGeneProductENSG00000111276 (Ensembl)
CHEK1GeneProductENSG00000149554 (Ensembl)
CHEK2GeneProductENSG00000183765 (Ensembl)
CREBGeneProduct1385 (Entrez Gene)
CYCSGeneProductENSG00000172115 (Ensembl)
CaffeineMetabolite2424 (Chemspider)
Cell CyclePathwayWP179 (WikiPathways)
DDB2GeneProductENSG00000134574 (Ensembl)
E2F1GeneProductENSG00000101412 (Ensembl)
EstradiolMetabolite16469 (ChEBI)
FANCD2GeneProductENSG00000144554 (Ensembl)
FASGeneProductENSG00000026103 (Ensembl)
GADD45AGeneProductENSG00000116717 (Ensembl)
GADD45BGeneProductENSG00000099860 (Ensembl)
GADD45GGeneProductENSG00000130222 (Ensembl)
H2AFXGeneProductENSG00000188486 (Ensembl)
HUS1GeneProductENSG00000188996 (Ensembl)
MDM2GeneProductENSG00000135679 (Ensembl)
MRE11GeneProduct4361 (Entrez Gene)
NBNGeneProduct4683 (Entrez Gene)
PIDDGeneProduct55367 (Entrez Gene)
PMAIP1GeneProductENSG00000141682 (Ensembl)
PMLGeneProductENSG00000140464 (Ensembl)
PRKDCGeneProductENSG00000121031 (Ensembl)
RAD17GeneProductENSG00000152942 (Ensembl)
RAD1GeneProductENSG00000113456 (Ensembl)
RAD50GeneProductENSG00000113522 (Ensembl)
RAD51GeneProductENSG00000051180 (Ensembl)
RAD52GeneProductENSG00000002016 (Ensembl)
RAD9AGeneProductENSG00000172613 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RFCGeneProduct5981 (Entrez Gene)
RPA2GeneProductENSG00000117748 (Ensembl)
RRM2BGeneProductENSG00000048392 (Ensembl)
SESN1GeneProductENSG00000080546 (Ensembl)
SFNGeneProductENSG00000175793 (Ensembl)
SMC1AGeneProductENSG00000072501 (Ensembl)
SenescencePathwayWP615 (WikiPathways)
TLK1GeneProductENSG00000198586 (Ensembl)
TLK2GeneProductENSG00000146872 (Ensembl)
TNFRSF10BGeneProductENSG00000120889 (Ensembl)
TP53AIP1GeneProductENSG00000120471 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
c-MycGeneProduct4609 (Entrez Gene)

Annotated Interactions

No annotated interactions

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