DNA Damage Response (Homo sapiens)

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612, 13641241141, 2, 8, 10, 14...12, 131911441, 2, 8, 10, 14...4121, 2, 8, 10, 14...1, 2, 8, 10, 14...41931941, 2, 8, 10, 14...4131941, 2, 8, 10, 14...441, 2, 8, 10, 14...4115, 7, 9, 10, 1512, 1361212, 1312, 13MitochondrionCaptionDNA repair9-1-1 complexDNA adductG2/M transitionChromatin alterationActivationBlocked replicationG2/M checkpointChromatinremodellingG2/M CheckpointROSCell-cycle progressionEndogenous:Collapsed replication forksSingle stranded DNA replication breaksFree radicals (ROS)InhibitionChange in cell conditionDNA damage sourceDouble-strand breaksSpecialized:Somatic hypermutaionV(D)J recombinationClass switchingReplication stressBlocked transcriptionBulky DNA lesionROSExogenous:Cigarette SmokeCaffeineRadiation (UV)ClastogenesHypoxiaGenotoxic drugsDNA repair anddamage preventionRB1DNA damage ATM dependentCell survivalCDC25CCASP8HUS1CCNB1MRE11CHEK1ATRCaffeineG1/S transitionCDKN1ARAD52c-MycCASP3MDM2CDK6DDB2PMLCCND3BIDTP53AIP1H2AFXRAD1FANCD2GADD45AFASPIDDCCND1Cell CycleRAD9ACYCSCDC2GADD45BRB1CDK57-hydroxystaurosporinePMAIP1CCNB3SESN1RAD51RRM2BCDKN1BCDK2GADD45GSFNATRIPBBC3RPA2RAD50TP53TLK1CDK4CCNE1TNFRSF10BGADD45GBAXRAD17BRCA1CHEK2SMC1AEstradiolCREBABL1E2F1PRKDCAPAF1CASP9CCNB2E2F1TLK2CDC25ANBNGADD45BCCNE2CCND2SenescenceGADD45AApoptosisalkylating agentsATMRFC


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 CPTAC Assay Portal

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Ontology Terms



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  7. 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 Europe PMC Scholia
  8. Sengupta S, Harris CC; ''p53: traffic cop at the crossroads of DNA repair and recombination.''; Nat Rev Mol Cell Biol, 2005 PubMed Europe PMC Scholia
  9. Pagano M, Jackson PK; ''Wagging the dogma; tissue-specific cell cycle control in the mouse embryo.''; Cell, 2004 PubMed Europe PMC Scholia
  10. Boutros R, Lobjois V, Ducommun B; ''CDC25 phosphatases in cancer cells: key players? Good targets?''; Nat Rev Cancer, 2007 PubMed Europe PMC Scholia
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110587view20:47, 19 May 2020Khanspersupdated complexes, legend
107190view14:27, 17 September 2019MaintBotChEBI identifier normalization
106373view00:56, 23 August 2019KhanspersModified description
105499view05:53, 8 August 2019KhanspersModified description
105227view01:43, 23 July 2019Khansperssimplified legend, updated colors/layout, added cell shape etc
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
30034view09:44, 29 June 2009I379077Specify description
29860view08:48, 8 June 2009I379077Caption
29694view07:29, 28 May 2009I379077Modified description
29693view07:28, 28 May 2009I379077Modified description
29682view08:30, 27 May 2009I379077Specify description
29674view09:09, 26 May 2009I379077Reverted to version '07:07, 25 May 2009' by I379077
29673view08:41, 26 May 2009I379077Specify description
29672view08:41, 26 May 2009I379077cell propertiez
29658view07:07, 25 May 2009I379077Specify description
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29525view07:21, 12 May 2009I379077Caption
29461view15:02, 8 May 2009I379077Specify description
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29459view14:31, 8 May 2009I379077Specify description
29458view10:03, 8 May 2009I379077Specify description
29457view09:40, 8 May 2009I379077Periodical save, work in progress
29450view14:53, 7 May 2009I379077Specify description
29449view14:51, 7 May 2009I379077Specify description

External references


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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)
Cell survivalPathway
DDB2GeneProductENSG00000134574 (Ensembl)
DNA damage ATM dependentPathwayWP710 (WikiPathways)
DNA repair and damage preventionPathway
E2F1GeneProductENSG00000101412 (Ensembl)
EstradiolMetaboliteCHEBI:16469 (ChEBI)
FANCD2GeneProductENSG00000144554 (Ensembl)
FASGeneProductENSG00000026103 (Ensembl)
G1/S transitionPathwayWP45 (WikiPathways)
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)
PRKDCGeneProductENSG00000253729 (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)
alkylating agentsMetaboliteCHEBI:22333 (ChEBI)
c-MycGeneProduct4609 (Entrez Gene)

Annotated Interactions

No annotated interactions

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