Skip to main content
SpringerLink
Log in

CHEK2

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

Synonyms

CDS1; CHK2; RAD53

Historical Background

Every day, each cell of our body is subjected to up to 1 million DNA lesions. These alterations are induced by genotoxic agents (e.g., chemicals, radiations), harmful metabolites, or DNA replication mistakes.

To prevent the replication of cells with damaged DNA, all organisms have evolved repair mechanisms that, in eukaryotes, are called the DNA-damage response (DDR). DDR is a network of molecular pathways that detect DNA lesions and, depending on the severity, arrest the cell cycle at checkpoints, repair DNA or, in presence of irreparable damage, initiate a program of permanent duplication arrest (senescence) or cellular suicide (apoptosis) (Ciccia and Elledge 2010).

In human cells, the activation of the DDR (Fig. 1) is promoted when sensor proteins find structural distortions or breaks on the DNA and attract to these sites the serine/threonine-protein kinase ATM (also called ataxia-telangiectasia mutated) and the...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Ahn JY, Li X, Davis HL, Canman CE. Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J Biol Chem. 2002;277(22):19389–95.

    Article  CAS  PubMed  Google Scholar 

  • Bucher N, Britten CD. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. Br J Cancer. 2008;98(3):523–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castedo M, Perfettini JL, Roumier T, Yakushijin K, Horne D, Medema R, et al. The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe. Oncogene. 2004;23(25):4353–61.

    Article  CAS  PubMed  Google Scholar 

  • Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell. 2010;40(2):179–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomez-Lazaro M, Fernandez-Gomez FJ, Jordan J. P53: Twenty Five Years Understanding the Mechanism of Genome Protection. J Physiol Biochem. 2004;60(4):287–307.

    Article  CAS  PubMed  Google Scholar 

  • Gorgoulis VG, Halazonetis TD. Oncogene-induced senescence: the bright and dark side of the response. Curr Opin Cell Biol. 2010;22(6):816–27.

    Article  CAS  PubMed  Google Scholar 

  • Lieber MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010;79:181–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magni M, Ruscica V, Restelli M, Fontanella E, Buscemi G, Zannini L. CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage. Oncotarget. 2015;6(19):17817–31.

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsuoka S, Huang M, Elledge SJ. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science. 1998;282(5395):1893–7.

    Article  CAS  PubMed  Google Scholar 

  • Maya-Mendoza A, Petermann E, Gillespie DA, Caldecott KW, Jackson DA. Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J. 2007;26(11):2719–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Momcilovic O, Knobloch L, Fornsaglio J, Varum S, Easley C, Schatten G. DNA damage responses in human induced pluripotent stem cells and embryonic stem cells. PLoS One. 2010;5(10):e13410.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sancar A, Lindsey-Boltz LA, Kang TH, Reardon JT, Lee JH, Ozturk N. Circadian clock control of the cellular response to DNA damage. FEBS Lett. 2010;584(12):2618–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schroeder EA, Raimundo N, Shadel GS. Epigenetic silencing mediates mitochondria stress-induced longevity. Cell Metab. 2013;17(6):954–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stolz A, Ertych N, Bastians H. Loss of the tumour-suppressor genes CHK2 and BRCA1 results in chromosomal instability. Biochem Soc Trans. 2010;38(6):1704–8.

    Article  CAS  PubMed  Google Scholar 

  • Tan Y, Raychaudhuri P, Costa RH. Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes. Mol Cell Biol. 2007;27(3):1007–16.

    Article  CAS  PubMed  Google Scholar 

  • Turnell AS, Grand RJ. DNA viruses and the cellular DNA-damage response. J Gen Virol. 2012;93(Pt 10):2076–97.

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Webster SR, Chen J. Characterization of tumor-associated Chk2 mutations. J Biol Chem. 2001;276(4):2971–4.

    Article  CAS  PubMed  Google Scholar 

  • Zannini L, Delia D, Buscemi G. CHK2 kinase in the DNA damage response and beyond. J Mol Cell Biol. 2014;6(6):442–57.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biosciences, Università degli Studi di Milano, Milan, Italy

    Giacomo Buscemi

  2. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Laura Zannini

Authors
  1. Giacomo Buscemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Zannini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giacomo Buscemi .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Buscemi, G., Zannini, L. (2016). CHEK2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101559-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101559-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation