title: H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy.
abstract: Double-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left unrepaired, may have severe consequences for cell survival, as they lead to chromosome aberrations, genomic instability, or cell death. Various physical, chemical, and biological factors are involved in DSB induction. Cells respond to DNA damage by activating the so-called DNA damage response (DDR), a complex molecular mechanism developed to detect and repair DNA damage. The formation of DSBs triggers activation of many factors, including phosphorylation of the histone variant H2AX, producing gammaH2AX. Phosphorylation of H2AX plays a key role in DDR and is required for the assembly of DNA repair proteins at the sites containing damaged chromatin as well as for activation of checkpoints proteins which arrest the cell cycle progression. In general, analysis of gammaH2AX expression can be used to detect the genotoxic effect of different toxic substances. When applied to clinical samples from cancer patients, evaluation of gammaH2AX levels may allow not only to monitor the efficiency of anticancer treatment but also to predict of tumor cell sensitivity to DNA damaging anticancer agents and toxicity of anticancer treatment toward normal cells.
authors.affiliation: Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20081 Lublin, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Podhorecka
authors.forename: Andrzej
authors.initials: A
authors.lastname: Skladanowski
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Bozko
references.citation: Genes Chromosomes Cancer. 2007 Aug;46(8):761-75
references.pmid: 17492757
references.citation: Cancer Lett. 2005 Nov 18;229(2):171-9
references.pmid: 16129552
references.citation: J Biol Chem. 2003 May 30;278(22):19579-82
references.pmid: 12697768
references.citation: Carcinogenesis. 2002 May;23(5):687-96
references.pmid: 12016139
references.citation: J Biol Chem. 2004 Mar 12;279(11):9677-80
references.pmid: 14742437
references.citation: DNA Repair (Amst). 2006 May 10;5(5):575-90
references.pmid: 16567133
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: Mol Cell Biol. 2005 Jul;25(13):5363-79
references.pmid: 15964794
references.citation: Cell. 2003 Aug 8;114(3):371-383
references.pmid: 12914701
references.citation: Nature. 2001 Dec 6;414(6864):660-665
references.pmid: 11740565
references.citation: Nat Rev Cancer. 2006 Oct;6(10):789-802
references.pmid: 16990856
references.citation: DNA Repair (Amst). 2005 Sep 28;4(10):1172-81
references.pmid: 16046194
references.citation: Science. 2003 Oct 24;302(5645):639-42
references.pmid: 14576433
references.citation: Curr Biol. 2005 Feb 8;15(3):R99-R102
references.pmid: 15694301
references.citation: Mol Cell. 2008 Jul 25;31(2):167-77
references.pmid: 18657500
references.citation: Nat Struct Mol Biol. 2006 May;13(5):451-7
references.pmid: 16622404
references.citation: Nat Rev Mol Cell Biol. 2000 Dec;1(3):179-86
references.pmid: 11252893
references.citation: Cell Prolif. 2007 Feb;40(1):1-13
references.pmid: 17227291
references.citation: Nature. 2003 Feb 27;421(6926):952-6
references.pmid: 12607003
references.citation: J Cell Biol. 2000 Dec 25;151(7):1381-90
references.pmid: 11134068
references.citation: Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95
references.pmid: 10959836
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13182-7
references.pmid: 16141325
references.citation: DNA Repair (Amst). 2006 Sep 8;5(9-10):1021-9
references.pmid: 16807135
references.citation: Science. 2007 May 25;316(5828):1160-6
references.pmid: 17525332
references.citation: Cytometry A. 2007 Sep;71(9):648-61
references.pmid: 17622968
references.citation: J Exp Med. 2003 Jun 16;197(12):1767-78
references.pmid: 12810694
references.citation: Cell Cycle. 2006 Dec;5(24):2909-13
references.pmid: 17172873
references.citation: Mol Cell. 1999 Sep;4(3):387-94
references.pmid: 10518219
references.citation: Semin Immunol. 1997 Jun;9(3):189-97
references.pmid: 9200330
references.citation: EMBO Rep. 2008 Aug;9(8):795-801
references.pmid: 18583988
references.citation: Chem Rev. 2009 Jul;109(7):2894-902
references.pmid: 19476377
references.citation: Nature. 2005 Mar 31;434(7033):605-11
references.pmid: 15758953
references.citation: Nat Struct Mol Biol. 2004 Jun;11(6):519-25
references.pmid: 15133503
references.citation: Cell Cycle. 2006 Sep;5(17):1940-5
references.pmid: 16940754
references.citation: Biochem Biophys Res Commun. 2005 Oct 28;336(3):807-12
references.pmid: 16153602
references.citation: Nat Rev Mol Cell Biol. 2002 Jun;3(6):430-40
references.pmid: 12042765
references.citation: Mutagenesis. 2007 Nov;22(6):395-401
references.pmid: 17855733
references.citation: DNA Repair (Amst). 2004 Aug-Sep;3(8-9):855-61
references.pmid: 15279770
references.citation: Nat Rev Cancer. 2009 May;9(5):327-37
references.pmid: 19377505
references.citation: Cancer Res. 2007 Mar 15;67(6):2685-92
references.pmid: 17363589
references.citation: J Cell Biol. 2009 May 18;185(4):577-86
references.pmid: 19451271
references.citation: Nature. 2003 Jan 30;421(6922):499-506
references.pmid: 12556884
references.citation: Cancer Res. 2003 Jun 1;63(11):2705-15
references.pmid: 12782571
references.citation: Breast Cancer Res Treat. 2008 Jul;110(2):357-66
references.pmid: 17851762
references.citation: Nucleic Acids Res. 2009 Feb;37(3):738-48
references.pmid: 19042970
references.citation: Mutagenesis. 2008 May;23(3):143-51
references.pmid: 18283046
references.citation: Nature. 2005 Apr 14;434(7035):864-70
references.pmid: 15829956
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8173-8
references.pmid: 12034884
references.citation: Science. 2002 May 3;296(5569):922-7
references.pmid: 11934988
references.citation: Cell. 2003 Aug 8;114(3):359-70
references.pmid: 12914700
references.citation: Cell Cycle. 2004 Feb;3(2):149-53
references.pmid: 14712078
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12871-6
references.pmid: 14566050
references.citation: J Biol Chem. 2001 Dec 21;276(51):47759-62
references.pmid: 11673449
references.citation: Cell. 2005 Dec 29;123(7):1213-26
references.pmid: 16377563
references.citation: Mol Cell. 2006 Jan 20;21(2):201-14
references.pmid: 16427010
references.citation: J Biol Chem. 2002 Nov 22;277(47):45149-53
references.pmid: 12228239
references.citation: Curr Cancer Drug Targets. 2006 May;6(3):197-205
references.pmid: 16712457
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1098-106
references.pmid: 17548670
references.citation: Nature. 2003 Feb 27;421(6926):961-6
references.pmid: 12607005
references.citation: Biochem Soc Trans. 2009 Aug;37(Pt 4):914-7
references.pmid: 19614618
references.citation: In Vivo. 2008 May-Jun;22(3):305-9
references.pmid: 18610740
references.citation: Cell Div. 2006 May 17;1(1):7
references.pmid: 16759429
references.citation: Mol Cell. 2004 Dec 22;16(6):1017-25
references.pmid: 15610743
references.citation: DNA Repair (Amst). 2006 May 10;5(5):534-43
references.pmid: 16531125
references.citation: Oncogene. 2007 Sep 6;26(41):6002-9
references.pmid: 17384674
references.citation: Nature. 2008 May 29;453(7195):682-6
references.pmid: 18438399
references.citation: Methods Mol Biol. 2006;314:81-93
references.pmid: 16673876
references.citation: Annu Rev Biochem. 1996;65:635-92
references.pmid: 8811192
references.citation: J Cell Biol. 2008 Jun 2;181(5):727-35
references.pmid: 18504301
references.citation: Curr Biol. 2001 Jun 26;11(12):991-5
references.pmid: 11448778
references.citation: Science. 2008 Mar 7;319(5868):1352-5
references.pmid: 18323444
references.citation: Science. 2005 Aug 5;309(5736):886-7
references.pmid: 16081723
references.citation: Mol Cell. 2006 Jan 20;21(2):187-200
references.pmid: 16427009
references.citation: J Biol Chem. 2004 Jan 16;279(3):2273-80
references.pmid: 14561744
references.citation: Dev Cell. 2001 Dec;1(6):759-70
references.pmid: 11740938
references.citation: Cell Prolif. 2005 Aug;38(4):223-43
references.pmid: 16098182
references.citation: Biochem Soc Trans. 2009 Jun;37(Pt 3):569-76
references.pmid: 19442252
references.citation: Nat Struct Mol Biol. 2007 Nov;14(11):1025-1040
references.pmid: 17984965
references.citation: Mol Cell Biol. 2009 Dec;29(24):6335-40
references.pmid: 19805510
references.citation: Biochem Biophys Res Commun. 1984 Aug 30;123(1):291-8
references.pmid: 6477583
references.citation: Nature. 2006 Mar 2;440(7080):105-9
references.pmid: 16400328
references.citation: J Biol Chem. 2003 Dec 26;278(52):52914-8
references.pmid: 14578343
references.citation: Curr Biol. 2002 Oct 29;12(21):1846-51
references.pmid: 12419185
references.citation: Mutat Res. 2007 Oct 1;623(1-2):83-97
references.pmid: 17681352
references.citation: Science. 2003 Oct 24;302(5645):636-9
references.pmid: 14576432
references.citation: Oncogene. 2007 Dec 10;26(56):7765-72
references.pmid: 18066089
references.citation: Biochem Soc Trans. 2001 Nov;29(Pt 6):655-61
references.pmid: 11709049
references.citation: Nat Struct Mol Biol. 2004 Jun;11(6):512-8
references.pmid: 15133502
references.citation: Mol Biol Cell. 2005 Oct;16(10):5013-25
references.pmid: 16030261
references.citation: J Biol Chem. 1998 Mar 6;273(10):5858-68
references.pmid: 9488723
references.citation: Nucleic Acids Res. 2008 Oct;36(17):5678-94
references.pmid: 18772227
references.citation: N Engl J Med. 1993 Sep 23;329(13):909-14
references.pmid: 8361504
references.citation: EMBO J. 2004 Jul 7;23(13):2674-83
references.pmid: 15201865
references.citation: Mol Cell Biol. 2007 Dec;27(24):8502-9
references.pmid: 17923702
references.citation: Mutat Res. 2009 Mar-Jun;681(2-3):180-188
references.pmid: 18804552
references.citation: Nature. 2005 Apr 14;434(7035):907-13
references.pmid: 15829965
references.citation: J Cell Physiol. 2005 Feb;202(2):492-502
references.pmid: 15389585
references.citation: J Biol Chem. 2005 Jan 14;280(2):1186-92
references.pmid: 15533933