DNA damage response (Homo sapiens)

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151, 3, 4, 9, 11...161616161651, 3, 4, 9, 11...16175, 681, 3, 4, 9, 11...5, 62, 7, 10, 13, 1481, 3, 4, 9, 11...16161, 3, 4, 9, 11...816517161619165, 6655, 61, 3, 4, 9, 11...1716175, 6151, 3, 4, 9, 11...15ActivationChange in the Cell conditionBlocked transcriptionCell-cycle progressionSpecialized:Somatic hypermutaionV(D)J recombinationClass switchingG1/S transitionMembraneDNA adductAlkylating agentsChromatin alterationDNA repairCellReplication stressDNA damage ATM dependentEndogenous:Collapsed replication forksSingle stranded DNA replication breaksFree radicals (ROS)MetaboliteG2/M transitionDNA repair and damage preventionCell survivalROSG2/M checkpointInhibitionExogenous:Cigarette SmokeCaffeineRadiation (UV)ClastogenesHypoxiaGenotoxic drugsGene productG2–MCheckpointDNA damage sourceDifferent pathwayBulky DNA lesionmitoch-ondrionBlocked replicationChromatinremodellingROSDouble-strand breaksCaption:Extral cellularSpaceCDKN1AGADD45GTLK2RB1RAD17GADD45BCDK2c-MycCDC25CSFNCCND3CDK5CCNE1CDC2CDK4CCNE2EstradiolRAD1PMAIP1CDK6TLK1RAD51CaffeineATMRFCGADD45BCDC25AFANCD2CASP8RRM2BDDB2CCNB1BIDRAD52ABL1RB1GADD45ABAXCREBCDKN1BTP53CCND2CCND1PRKDCMRE11RPA2GADD45GCell CycleSESN1TNFRSF10BCCNB2H2AFXBBC3ATRGADD45AE2F1FASCHEK1HUS1APAF1SenescenceApoptosisPIDDCCNB3CASP9MDM2CHEK2TP53AIP1CYCSATRIP7-hydroxystaurosporineSMC1ABRCA1CASP3RAD50E2F1RAD9ANBNPML


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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  1. Harrison JC, Haber JE; ''Surviving the breakup: the DNA damage checkpoint.''; Annu Rev Genet, 2006 PubMed Europe PMC Scholia
  2. Löbrich M, Jeggo PA; ''The impact of a negligent G2/M checkpoint on genomic instability and cancer induction.''; Nat Rev Cancer, 2007 PubMed Europe PMC Scholia
  3. Sparmann A, van Lohuizen M; ''Polycomb silencers control cell fate, development and cancer.''; Nat Rev Cancer, 2006 PubMed Europe PMC Scholia
  4. 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 Europe PMC Scholia
  5. 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 Europe PMC Scholia
  6. Cory S, Huang DC, Adams JM; ''The Bcl-2 family: roles in cell survival and oncogenesis.''; Oncogene, 2003 PubMed Europe PMC Scholia
  7. Vousden KH, Lane DP; ''p53 in health and disease.''; Nat Rev Mol Cell Biol, 2007 PubMed Europe PMC Scholia
  8. Toledo F, Wahl GM; ''Regulating the p53 pathway: in vitro hypotheses, in vivo veritas.''; Nat Rev Cancer, 2006 PubMed Europe PMC Scholia
  9. Ljungman M, Lane DP; ''Transcription - guarding the genome by sensing DNA damage.''; Nat Rev Cancer, 2004 PubMed Europe PMC Scholia
  10. 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
  11. Strasser A; ''The role of BH3-only proteins in the immune system.''; Nat Rev Immunol, 2005 PubMed Europe PMC Scholia
  12. Pagano M, Jackson PK; ''Wagging the dogma; tissue-specific cell cycle control in the mouse embryo.''; Cell, 2004 PubMed Europe PMC Scholia
  13. Gong H, Cao Y, Han G, Zhang Y, You Q, Wang Y, Pan Y; ''p53/microRNA-374b/AKT1 regulates colorectal cancer cell apoptosis in response to DNA damage''; DOI: 10.3892/ijo.2017.3922, 2017 PubMed Europe PMC Scholia
  14. Wang W; ''Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins.''; Nat Rev Genet, 2007 PubMed Europe PMC Scholia
  15. 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
  16. Boutros R, Lobjois V, Ducommun B; ''CDC25 phosphatases in cancer cells: key players? Good targets?''; Nat Rev Cancer, 2007 PubMed Europe PMC Scholia
  17. 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 Europe PMC Scholia
  18. Sherr CJ, Roberts JM; ''Living with or without cyclins and cyclin-dependent kinases.''; Genes Dev, 2004 PubMed Europe PMC Scholia
  19. Reshmi SC, Gollin SM; ''Chromosomal instability in oral cancer cells.''; J Dent Res, 2005 PubMed Europe PMC Scholia
  20. Zhou BB, Bartek J; ''Targeting the checkpoint kinases: chemosensitization versus chemoprotection.''; Nat Rev Cancer, 2004 PubMed Europe PMC Scholia


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124174view12:52, 23 September 2022VanessaSousaAKT1 gene is involved in DNA damage response
116541view12:11, 7 May 2021EweitzModified title
113795view10:06, 24 November 2020Finterlysmall graphical update
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
29583view08:18, 19 May 2009I379077Specify description
29555view07:41, 15 May 2009I379077Specify description
29542view09:04, 14 May 2009I379077Specify description
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29526view07:23, 12 May 2009I379077Specify description
29525view07:21, 12 May 2009I379077Caption
29461view15:02, 8 May 2009I379077Specify description
29460view14:54, 8 May 2009I379077Specify description
29459view14:31, 8 May 2009I379077Specify description
29458view10:03, 8 May 2009I379077Specify description

External references


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

Annotated Interactions

No annotated interactions

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