H2AX

Summary

Gene Symbol: H2AX
Description: H2A histone family member X
Alias: H2A.X, H2A/X, H2AX, histone H2AX, H2AX histone, histone H2A.x
Species: human
Products:     H2AX

Top Publications

  1. Paull T, Rogakou E, Yamazaki V, Kirchgessner C, Gellert M, Bonner W. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol. 2000;10:886-95 pubmed
    ..Recently it has been reported that a member of the histone H2A family, H2AX, becomes extensively phosphorylated within 1-3 minutes of DNA damage and forms foci at break sites...
  2. Redon C, Nakamura A, Zhang Y, Ji J, Bonner W, Kinders R, et al. Histone gammaH2AX and poly(ADP-ribose) as clinical pharmacodynamic biomarkers. Clin Cancer Res. 2010;16:4532-42 pubmed publisher
    ..Because DSBs induce the phosphorylation of histone H2AX (γH2AX) in the chromatin flanking the break site, an antibody directed against γH2AX can be employed to ..
  3. Bakkenist C, Kastan M. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature. 2003;421:499-506 pubmed
  4. Burdak Rothkamm S, Short S, Folkard M, Rothkamm K, Prise K. ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. Oncogene. 2007;26:993-1002 pubmed
    ..Furthermore, ATR-dependent bystander foci induction was restricted to S-phase cells. These observations may provide additional therapeutic targets for the exploitation of the bystander effect. ..
  5. Ward I, Minn K, Jorda K, Chen J. Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. J Biol Chem. 2003;278:19579-82 pubmed
    ..in the DNA damage response, 53BP1 becomes hyperphosphorylated after radiation and colocalizes with phosphorylated H2AX in megabase regions surrounding the sites of DNA strand breaks...
  6. Mischo H, Hemmerich P, Grosse F, Zhang S. Actinomycin D induces histone gamma-H2AX foci and complex formation of gamma-H2AX with Ku70 and nuclear DNA helicase II. J Biol Chem. 2005;280:9586-94 pubmed
    Formation of gamma-H2AX foci is a P. O.cellular response to genotoxic stress, such as DNA double strand breaks or stalled replication forks. Here we show that gamma-H2AX foci were also formed when cells were incubated with 0...
  7. Park E, Chan D, Park J, Oettinger M, Kwon J. DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner. Nucleic Acids Res. 2003;31:6819-27 pubmed
    ..ability of Ku to bind to the ends of nucleosomal DNA, and that the activated DNA-PK is capable of phosphorylating H2AX within the nucleosomes...
  8. Li A, Yu Y, Lee S, Ishibashi T, Lees Miller S, Ausio J. Phosphorylation of histone H2A.X by DNA-dependent protein kinase is not affected by core histone acetylation, but it alters nucleosome stability and histone H1 binding. J Biol Chem. 2010;285:17778-88 pubmed publisher
    ..Finally, we show that although H2A.X does not affect nucleosome conformation, it has a de-stabilizing effect that is enhanced by the DNA-PK-mediated phosphorylation and results in an impaired histone H1 binding. ..
  9. Banath J, Klokov D, Macphail S, Banuelos C, Olive P. Residual gammaH2AX foci as an indication of lethal DNA lesions. BMC Cancer. 2010;10:4 pubmed publisher

More Information

Publications91

  1. Vasireddy R, Karagiannis T, El Osta A. gamma-radiation-induced gammaH2AX formation occurs preferentially in actively transcribing euchromatic loci. Cell Mol Life Sci. 2010;67:291-4 pubmed publisher
    ..Here, we have extended those studies and provide evidence that gammaH2AX foci form preferentially in actively transcribing euchromatin following gamma-irradiation...
  2. Ichijima Y, Sakasai R, Okita N, Asahina K, Mizutani S, Teraoka H. Phosphorylation of histone H2AX at M phase in human cells without DNA damage response. Biochem Biophys Res Commun. 2005;336:807-12 pubmed
    A variant of histone H2A, H2AX, is phosphorylated on Ser139 in response to DNA double-strand breaks (DSBs), and clusters of the phosphorylated form of H2AX (gamma-H2AX) in nuclei of DSB-induced cells show foci at breakage sites...
  3. Tanaka T, Kajstura M, Halicka H, Traganos F, Darzynkiewicz Z. Constitutive histone H2AX phosphorylation and ATM activation are strongly amplified during mitogenic stimulation of lymphocytes. Cell Prolif. 2007;40:1-13 pubmed
    We recently postulated that constitutive activation of Ataxia Telangiectasia, Mutated (CAA) and constitutive histone H2AX phosphorylation (CHP) seen in cells not treated with genotoxic agents are the events triggered by DNA damage caused ..
  4. Wu C, Kang H, Yang W, Wu J, Jeong Y, Wang J, et al. Critical role of monoubiquitination of histone H2AX protein in histone H2AX phosphorylation and DNA damage response. J Biol Chem. 2011;286:30806-15 pubmed publisher
    ..Histone variant H2AX is a critical sensor that undergoes phosphorylation at serine 139 upon genotoxic stress, which provides a docking ..
  5. Fernandez Capetillo O, Chen H, Celeste A, Ward I, Romanienko P, Morales J, et al. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol. 2002;4:993-7 pubmed
    ..b>Histone H2AX, p53 binding-protein 1 (53BP1) and Chk2 are targets of ATM-mediated phosphorylation, but little is known about ..
  6. Peng A, Chen P. NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage. J Biol Chem. 2003;278:8873-6 pubmed
    ..NFBD1 associates with nuclear foci within minutes following IR, a property similar to histone H2AX, 53BP1, and Chk2, which are all early participants in the DNA damage signaling cascade...
  7. Mannironi C, Bonner W, Hatch C. H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals. Nucleic Acids Res. 1989;17:9113-26 pubmed
    ..The short form behaves as a replication type histone mRNA, decreasing in amount when cell cultures are incubated with inhibitors of DNA synthesis, while the longer behaves as a basal type histone mRNA. ..
  8. Srivastava N, Gochhait S, Gupta P, Bamezai R. Copy number alterations of the H2AFX gene in sporadic breast cancer patients. Cancer Genet Cytogenet. 2008;180:121-8 pubmed publisher
    In addition to being a structural component of chromatin, histone H2AX also has an important role in preserving genetic integrity. The histone H2AFX gene maps to the chromosome region 11q23.2 approximately 11q23...
  9. Sengupta S, Robles A, Linke S, Sinogeeva N, Zhang R, Pedeux R, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol. 2004;166:801-13 pubmed
    ..BLM colocalized and physically interacted with the DNA damage response proteins 53BP1 and H2AX. Although BLM facilitated physical interaction between p53 and 53BP1, 53BP1 was required for efficient accumulation ..
  10. Chowdhury D, Keogh M, Ishii H, Peterson C, Buratowski S, Lieberman J. gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell. 2005;20:801-9 pubmed
    Phosphorylated histone H2AX (gamma-H2AX) forms foci over large chromatin domains surrounding double-stranded DNA breaks (DSB). These foci recruit DSB repair proteins and dissolve during or after repair is completed...
  11. Mailand N, Bekker Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell. 2007;131:887-900 pubmed
    ..In addition, we show that RNF8 can ubiquitylate histone H2A and H2AX, and that its depletion sensitizes cells to ionizing radiation...
  12. Rogakou E, Pilch D, Orr A, Ivanova V, Bonner W. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858-68 pubmed
    ..acid-urea-cetyltrimethylammonium bromide gels after exposure of cells to ionizing radiation, are shown to be histone H2AX species that have been phosphorylated specifically at serine 139...
  13. Heo K, Kim H, Choi S, Choi J, Kim K, Gu J, et al. FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16. Mol Cell. 2008;30:86-97 pubmed publisher
    The phosphorylation of histone variant H2AX at DNA double-strand breaks is believed to be critical for recognition and repair of DNA damage...
  14. Kobayashi J, Tauchi H, Sakamoto S, Nakamura A, Morishima K, Matsuura S, et al. NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain. Curr Biol. 2002;12:1846-51 pubmed
    ..breakage syndrome (NBS), physically interacts with histone, rather than damaged DNA, by direct binding to gamma-H2AX. We also demonstrate that NBS1 binding can occur in the absence of interaction with hMRE11 or BRCA1...
  15. Schmid T, Dollinger G, Beisker W, Hable V, Greubel C, Auer S, et al. Differences in the kinetics of gamma-H2AX fluorescence decay after exposure to low and high LET radiation. Int J Radiat Biol. 2010;86:682-91 pubmed publisher
    ..We analysed the decay of the integrated fluorescence intensity of gamma-H2AX (phosphorylated histone H2AX) which is thought to reflect the repair kinetics of radiation-induced DNA double-strand breaks (DSB) using ..
  16. Cooper A, García M, Petrovas C, Yamamoto T, Koup R, Nabel G. HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature. 2013;498:376-9 pubmed publisher
    ..kinase (DNA-PK), a central integrator of the DNA damage response, which caused phosphorylation of p53 and histone H2AX. Pharmacological inhibition of DNA-PK abolished cell death during HIV-1 infection in vitro, suggesting that ..
  17. Lal A, Pan Y, Navarro F, Dykxhoorn D, Moreau L, Meire E, et al. miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat Struct Mol Biol. 2009;16:492-8 pubmed publisher
    ..is upregulated during postmitotic differentiation of hematopoietic cell lines and regulates the histone variant H2AX, a protein that has a key role in the double-stranded break response...
  18. Bewersdorf J, Bennett B, Knight K. H2AX chromatin structures and their response to DNA damage revealed by 4Pi microscopy. Proc Natl Acad Sci U S A. 2006;103:18137-42 pubmed
    ..Phosphorylation of histone H2AX to form gamma-H2AX is one of the earliest of these events and is important for coordination of signaling and ..
  19. Huang X, Tanaka T, Kurose A, Traganos F, Darzynkiewicz Z. Constitutive histone H2AX phosphorylation on Ser-139 in cells untreated by genotoxic agents is cell-cycle phase specific and attenuated by scavenging reactive oxygen species. Int J Oncol. 2006;29:495-501 pubmed
    DNA damage, particularly when it involves formation of double-strand breaks (DSBs), triggers phosphorylation of histone H2AX on Ser-139...
  20. Redon C, Pilch D, Rogakou E, Sedelnikova O, Newrock K, Bonner W. Histone H2A variants H2AX and H2AZ. Curr Opin Genet Dev. 2002;12:162-9 pubmed
    ..Recent studies have begun to elucidate the roles of two of the H2A variants, H2AX and H2AZ...
  21. Olive P, Banath J, Keyes M. Residual gammaH2AX after irradiation of human lymphocytes and monocytes in vitro and its relation to late effects after prostate brachytherapy. Radiother Oncol. 2008;86:336-46 pubmed
    ..However, it failed to predict for late normal tissue toxicity after brachytherapy. Possible reasons are discussed. ..
  22. Rogakou E, Nieves Neira W, Boon C, Pommier Y, Bonner W. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem. 2000;275:9390-5 pubmed
    b>Histone H2AX is a ubiquitous member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionarily conserved C-terminal motif, -KKATQASQEY...
  23. Mattiroli F, Vissers J, van Dijk W, Ikpa P, Citterio E, Vermeulen W, et al. RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell. 2012;150:1182-95 pubmed publisher
    ..DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination...
  24. Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, et al. A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol Cell. 2008;31:33-46 pubmed publisher
    The histone H2A variant H2AX is rapidly phosphorylated in response to DNA double-stranded breaks to produce gamma-H2AX. gamma-H2AX stabilizes cell-cycle checkpoint proteins and DNA repair factors at the break site...
  25. Liu Y, Parry J, Chin A, Duensing S, Duensing A. Soluble histone H2AX is induced by DNA replication stress and sensitizes cells to undergo apoptosis. Mol Cancer. 2008;7:61 pubmed publisher
    Chromatin-associated histone H2AX is a key regulator of the cellular responses to DNA damage. However, non-nucleosomal functions of histone H2AX are poorly characterized...
  26. Celeste A, Fernandez Capetillo O, Kruhlak M, Pilch D, Staudt D, Lee A, et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol. 2003;5:675-9 pubmed
    b>Histone H2AX is rapidly phosphorylated in the chromatin micro-environment surrounding a DNA double-strand break (DSB)...
  27. Halicka H, Huang X, Traganos F, King M, Dai W, Darzynkiewicz Z. Histone H2AX phosphorylation after cell irradiation with UV-B: relationship to cell cycle phase and induction of apoptosis. Cell Cycle. 2005;4:339-45 pubmed
    Damage to DNA that engenders double-strand breaks (DSBs) triggers phosphorylation of histone H2AX on Ser-139...
  28. Stiff T, O Driscoll M, Rief N, Iwabuchi K, Lobrich M, Jeggo P. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 2004;64:2390-6 pubmed
    b>H2AX phosphorylation is an early step in the response to DNA damage. It is widely accepted that ATM (ataxia telangiectasia mutated protein) phosphorylates H2AX in response to DNA double-strand breaks (DSBs)...
  29. Fragkos M, Jurvansuu J, Beard P. H2AX is required for cell cycle arrest via the p53/p21 pathway. Mol Cell Biol. 2009;29:2828-40 pubmed publisher
    Phosphorylation of H2AX (gammaH2AX) is an early sign of DNA damage induced by replication stalling. However, the role of H2AX in the repair of this type of DNA damage is still unclear...
  30. Ward I, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem. 2001;276:47759-62 pubmed
    b>H2AX, a member of the histone H2A family, is rapidly phosphorylated in response to ionizing radiation...
  31. Tanaka T, Kurose A, Huang X, Dai W, Darzynkiewicz Z. ATM activation and histone H2AX phosphorylation as indicators of DNA damage by DNA topoisomerase I inhibitor topotecan and during apoptosis. Cell Prolif. 2006;39:49-60 pubmed
    ..ATM) kinase through its auto- or trans-phosphorylation on Ser1981 and activated ATM is one of the mediators of histone H2AX phosphorylation on Ser139...
  32. Reitsema T, Klokov D, Banath J, Olive P. DNA-PK is responsible for enhanced phosphorylation of histone H2AX under hypertonic conditions. DNA Repair (Amst). 2005;4:1172-81 pubmed
    ..of cells to hypertonic medium after X-irradiation results in a 3-4-fold increase in the phosphorylation of histone H2AX (gammaH2AX) at sites of radiation-induced DNA double-strand breaks...
  33. Seo J, Kim S, Lee H, Kim J, Shon H, Salleh N, et al. Genome-wide profiles of H2AX and ?-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells. Nucleic Acids Res. 2012;40:5965-74 pubmed
    Phosphorylation of the histone variant H2AX forms ?-H2AX that marks DNA double-strand break (DSB)...
  34. Warters R, Adamson P, Pond C, Leachman S. Melanoma cells express elevated levels of phosphorylated histone H2AX foci. J Invest Dermatol. 2005;124:807-17 pubmed
    When human cells sustain a DNA double-strand break (dsb), histone H2AX in chromatin surrounding the DNA break is phosphorylated, marking repair foci...
  35. Mallery D, Vandenberg C, Hiom K. Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains. EMBO J. 2002;21:6755-62 pubmed
    ..First, it mediates the monoubiquitylation of nucleosome core histones in vitro, including the variant histone H2AX that co-localizes with BRCA1 at sites of DNA damage...
  36. Ginjala V, Nacerddine K, Kulkarni A, Oza J, Hill S, Yao M, et al. BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Mol Cell Biol. 2011;31:1972-82 pubmed publisher
    ..The sustained localization of BMI1 to damage sites is dependent on intact ATM and ATR and requires H2AX phosphorylation and recruitment of RNF8...
  37. Cook P, Ju B, Telese F, Wang X, Glass C, Rosenfeld M. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature. 2009;458:591-6 pubmed publisher
    ..the relative recruitment of either DNA repair or pro-apoptotic factors to the tail of serine phosphorylated histone H2AX (gamma-H2AX) and allows it to function as an active determinant of repair/survival versus apoptotic responses ..
  38. Nagelkerke A, van Kuijk S, Sweep F, Nagtegaal I, Hoogerbrugge N, Martens J, et al. Constitutive expression of ?-H2AX has prognostic relevance in triple negative breast cancer. Radiother Oncol. 2011;101:39-45 pubmed publisher
    Constitutive ?-H2AX expression might indicate disruption of the DNA damage repair pathway, genomic instability, or shortened telomeric ends...
  39. Huen M, Grant R, Manke I, Minn K, Yu X, Yaffe M, et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell. 2007;131:901-14 pubmed
    ..the phospho-dependent FHA domain-mediated binding of RNF8 to MDC1, on the other hand via its role in ubiquitylating H2AX and possibly other substrates at damage sites...
  40. Kato T, Nagasawa H, Weil M, Little J, Bedford J. Levels of gamma-H2AX Foci after low-dose-rate irradiation reveal a DNA DSB rejoining defect in cells from human ATM heterozygotes in two at families and in another apparently normal individual. Radiat Res. 2006;166:443-53 pubmed
    We have investigated the use of the gamma-H2AX assay, reflecting the presence of DNA double-strand breaks, as a possible means for identifying individuals who are mildly hypersensitive to ionizing radiation, such as some ATM heterozygotes...
  41. Cowell I, Sunter N, Singh P, Austin C, Durkacz B, Tilby M. gammaH2AX foci form preferentially in euchromatin after ionising-radiation. PLoS ONE. 2007;2:e1057 pubmed
    ..Using immunofluorescence microscopy, we show that focal phosphorylation of histone H2AX occurs preferentially in euchromatic regions of the genome following X-irradiation...
  42. Wasco M, Pu R, Yu L, Su L, Ma L. Expression of gamma-H2AX in melanocytic lesions. Hum Pathol. 2008;39:1614-20 pubmed publisher
    gamma-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and their precursor lesions...
  43. Lee J, Paull T. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science. 2004;304:93-6 pubmed
    ..We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX. MRN makes multiple contacts with ATM and appears to stimulate ATM activity by facilitating the stable binding ..
  44. Stucki M, Clapperton J, Mohammad D, Yaffe M, Smerdon S, Jackson S. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell. 2005;123:1213-26 pubmed
    Histone variant H2AX phosphorylation in response to DNA damage is the major signal for recruitment of DNA-damage-response proteins to regions of damaged chromatin...
  45. Siino J, Nazarov I, Svetlova M, Solovjeva L, Adamson R, Zalenskaya I, et al. Photobleaching of GFP-labeled H2AX in chromatin: H2AX has low diffusional mobility in the nucleus. Biochem Biophys Res Commun. 2002;297:1318-23 pubmed
    The Ser-139 phosphorylated form of replacement histone H2AX (gamma-H2AX) is induced within large chromatin domains by double-strand DNA breaks (DSBs) in mammalian chromosomes...
  46. Fernandez Capetillo O, Mahadevaiah S, Celeste A, Romanienko P, Camerini Otero R, Bonner W, et al. H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell. 2003;4:497-508 pubmed
    ..Here we show that the X and Y chromosomes of histone H2AX-deficient spermatocytes fail to condense to form a sex body, do not initiate MSCI, and exhibit severe defects ..
  47. Vasireddy R, Sprung C, Cempaka N, Chao M, McKay M. H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype. Br J Cancer. 2010;102:1511-8 pubmed publisher
    ..Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other ..
  48. Gagou M, Zuazua Villar P, Meuth M. Enhanced H2AX phosphorylation, DNA replication fork arrest, and cell death in the absence of Chk1. Mol Biol Cell. 2010;21:739-52 pubmed publisher
    b>H2AX phosphorylation at serine 139 (gammaH2AX) is a sensitive indicator of both DNA damage and DNA replication stress...
  49. Fernandez Capetillo O, Lee A, Nussenzweig M, Nussenzweig A. H2AX: the histone guardian of the genome. DNA Repair (Amst). 2004;3:959-67 pubmed
    ..But, thanks to its prime positioning, a variation in the tail of H2AX enables rapid modification of the histone code in response to DNA damage...
  50. Baure J, Izadi A, Suarez V, Giedzinski E, Cleaver J, Fike J, et al. Histone H2AX phosphorylation in response to changes in chromatin structure induced by altered osmolarity. Mutagenesis. 2009;24:161-7 pubmed publisher
    DNA strand breaks trigger marked phosphorylation of histone H2AX (i.e. gamma-H2AX)...
  51. Xiao A, Li H, Shechter D, Ahn S, Fabrizio L, Erdjument Bromage H, et al. WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature. 2009;457:57-62 pubmed publisher
    ..Our work demonstrates a new mechanism that regulates the DNA damage response and expands our knowledge of domains that contain intrinsic tyrosine kinase activity. ..
  52. Rogakou E, Boon C, Redon C, Bonner W. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999;146:905-16 pubmed
    ..breaks introduced into mammalian cells by ionizing radiation results in the specific phosphorylation of histone H2AX on serine residue 139, yielding a specific modified form named gamma-H2AX...
  53. Rothkamm K, Horn S. gamma-H2AX as protein biomarker for radiation exposure. Ann Ist Super Sanita. 2009;45:265-71 pubmed
    ..Here we discuss the usefulness of the DNA damage marker gamma-H2AX for this purpose...
  54. Riballo E, Kühne M, Rief N, Doherty A, Smith G, Recio M, et al. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Mol Cell. 2004;16:715-24 pubmed
    ..in patients with RS-SCID, function in a common double-strand break (DSB) repair pathway that also requires H2AX, 53BP1, Nbs1, Mre11, and DNA-PK. We show that radiation-induced Artemis hyperphosphorylation is ATM dependent...
  55. Yoshikawa T, Kashino G, Ono K, Watanabe M. Phosphorylated H2AX foci in tumor cells have no correlation with their radiation sensitivities. J Radiat Res. 2009;50:151-60 pubmed
    ..The histone H2AX is phosphorylated, and phosphorylated H2AX makes a focus...
  56. Banuelos C, Banath J, Kim J, Aquino Parsons C, Olive P. gammaH2AX expression in tumors exposed to cisplatin and fractionated irradiation. Clin Cancer Res. 2009;15:3344-53 pubmed publisher
    ..Use of residual gammaH2AX as a biomarker for response is feasible when cell survival exceeds approximately 20%, but heterogeneity in endogenous and treatment-induced gammaH2AX must be considered. ..
  57. Dickey J, Redon C, Nakamura A, Baird B, Sedelnikova O, Bonner W. H2AX: functional roles and potential applications. Chromosoma. 2009;118:683-92 pubmed publisher
    Upon DNA double-strand break (DSB) induction in mammals, the histone H2A variant, H2AX, becomes rapidly phosphorylated at serine 139...
  58. Bonner W, Redon C, Dickey J, Nakamura A, Sedelnikova O, Solier S, et al. GammaH2AX and cancer. Nat Rev Cancer. 2008;8:957-67 pubmed publisher
    b>Histone H2AX phosphorylation on a serine four residues from the carboxyl terminus (producing gammaH2AX) is a sensitive marker for DNA double-strand breaks (DSBs)...
  59. Chadwick B, Lane T. BRCA1 associates with the inactive X chromosome in late S-phase, coupled with transient H2AX phosphorylation. Chromosoma. 2005;114:432-9 pubmed
    ..A hallmark of these foci is the presence of S139 phosphorylated histone H2AX. BRCA1 was recently shown to associate with facultative heterochromatin at the inactive X chromosome (Xi), ..
  60. Werbrouck J, Duprez F, De Neve W, Thierens H. Lack of a correlation between ?H2AX foci kinetics in lymphocytes and the severity of acute normal tissue reactions during IMRT treatment for head and neck cancer. Int J Radiat Biol. 2011;87:46-56 pubmed publisher
    To investigate the phosphorylated histone H2A isoform X (?H2AX) foci kinetics as an indicator for the development of acute normal tissue complications during Intensity-Modulated Radiotherapy (IMRT) for head and neck cancer (HNC) patients...
  61. Herbig U, Jobling W, Chen B, Chen D, Sedivy J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14:501-13 pubmed
    ..Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals. ..
  62. Iacovoni J, Caron P, Lassadi I, Nicolas E, Massip L, Trouche D, et al. High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome. EMBO J. 2010;29:1446-57 pubmed publisher
  63. Marti T, Hefner E, Feeney L, Natale V, Cleaver J. H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks. Proc Natl Acad Sci U S A. 2006;103:9891-6 pubmed
    The variant histone H2AX is phosphorylated in response to UV irradiation of primary human fibroblasts in a complex fashion that is radically different from that commonly reported after DNA double-strand breaks...
  64. Kaneko H, Igarashi K, Kataoka K, Miura M. Heat shock induces phosphorylation of histone H2AX in mammalian cells. Biochem Biophys Res Commun. 2005;328:1101-6 pubmed
    ..In this communication, we present the first evidence that heat shock induces the phosphorylated form of histone H2AX, which is thought to be generated at the chromatin proximal to DSB sites...
  65. Kobayashi J, Tauchi H, Chen B, Burma S, Bruma S, Tashiro S, et al. Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1. Biochem Biophys Res Commun. 2009;380:752-7 pubmed publisher
    Phosphorylated histone H2AX (gamma-H2AX) functions in the recruitment of DNA damage response proteins to DNA double-strand breaks (DSBs) and facilitates DSB repair...
  66. Stewart G, Wang B, Bignell C, Taylor A, Elledge S. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature. 2003;421:961-6 pubmed
    ..It has recently been shown that the histone H2A variant H2AX specifically controls the recruitment of DNA repair proteins to the sites of DNA damage...
  67. Pan M, Peng G, Hung W, Lin S. Monoubiquitination of H2AX protein regulates DNA damage response signaling. J Biol Chem. 2011;286:28599-607 pubmed publisher
    ..In mammalian cells, a key component in this network is H2AX, which becomes rapidly phosphorylated at Ser(139) (?-H2AX) at DSBs...
  68. Burma S, Chen B, Murphy M, Kurimasa A, Chen D. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem. 2001;276:42462-7 pubmed
    A very early step in the response of mammalian cells to DNA double-strand breaks is the phosphorylation of histone H2AX at serine 139 at the sites of DNA damage...
  69. Chen W, Alpert A, Leiter C, Gong F, Jackson S, Miller K. Systematic identification of functional residues in mammalian histone H2AX. Mol Cell Biol. 2013;33:111-26 pubmed publisher
    The histone variant H2AX is a principal component of chromatin involved in the detection, signaling, and repair of DNA double-strand breaks (DSBs)...
  70. Matsumoto M, Yaginuma K, Igarashi A, Imura M, Hasegawa M, Iwabuchi K, et al. Perturbed gap-filling synthesis in nucleotide excision repair causes histone H2AX phosphorylation in human quiescent cells. J Cell Sci. 2007;120:1104-12 pubmed
    Human histone H2AX is rapidly phosphorylated on serine 139 in response to DNA double-strand breaks and plays a crucial role in tethering the factors involved in DNA repair and damage signaling...
  71. Roch Lefevre S, Mandina T, Voisin P, Gaëtan G, Mesa J, Valente M, et al. Quantification of gamma-H2AX foci in human lymphocytes: a method for biological dosimetry after ionizing radiation exposure. Radiat Res. 2010;174:185-94 pubmed publisher
    Recent studies have suggested that visualization of gamma-H2AX nuclear foci can be used to estimate exposure to very low doses of ionizing radiation...
  72. Lilley C, Chaurushiya M, Boutell C, Landry S, Suh J, Panier S, et al. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. EMBO J. 2010;29:943-55 pubmed publisher
    ..Our study raises the possibility that the ICP0-mediated control of histone ubiquitination may link DNA repair, relief of transcriptional repression, and activation of latent viral genomes. ..
  73. Lukas C, Melander F, Stucki M, Falck J, Bekker Jensen S, Goldberg M, et al. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J. 2004;23:2674-83 pubmed
    ..This occurred despite normal phosphorylation of H2AX, indicating that lack of Mdc1 does not impair this DSB-induced chromatin change, but rather precludes the sustained ..
  74. Park J, Park E, Lee H, Kim S, Hur S, Imbalzano A, et al. Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction. EMBO J. 2006;25:3986-97 pubmed
    ..inefficient DNA double-strand break (DSB) repair and increased DNA damage sensitivity as well as a large defect in H2AX phosphorylation (gamma-H2AX) and nuclear focus formation after DNA damage...
  75. Furuta T, Takemura H, Liao Z, Aune G, Redon C, Sedelnikova O, et al. Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J Biol Chem. 2003;278:20303-12 pubmed
    ..breaks originating from diverse causes in eukaryotic cells are accompanied by the formation of phosphorylated H2AX (gammaH2AX) foci...
  76. Wang H, Wang M, Wang H, Böcker W, Iliakis G. Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors. J Cell Physiol. 2005;202:492-502 pubmed
    ..DNA double strand breaks (DSBs) cause the prompt phosphorylation of serine 139 at the carboxy terminus of histone H2AX to generate gamma-H2AX, detectable by Western blotting or immunofluorescence...
  77. Al Rashid S, Dellaire G, Cuddihy A, Jalali F, Vaid M, Coackley C, et al. Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo. Cancer Res. 2005;65:10810-21 pubmed
    ..p53Ser15 colocalizes and coimmunoprecipitates with gamma-H2AX with kinetics similar to that of biochemical DNA double-strand break (DNA-dsb) rejoining...
  78. Suzuki M, Suzuki K, Kodama S, Watanabe M. Phosphorylated histone H2AX foci persist on rejoined mitotic chromosomes in normal human diploid cells exposed to ionizing radiation. Radiat Res. 2006;165:269-76 pubmed
    b>Histone H2AX is phosphorylated and forms foci in response to exposure to ionizing radiation...
  79. Ikura T, Tashiro S, Kakino A, Shima H, Jacob N, Amunugama R, et al. DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. Mol Cell Biol. 2007;27:7028-40 pubmed
    ..Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage...
  80. Chadwick B, Willard H. Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant. Hum Mol Genet. 2001;10:1101-13 pubmed
    ..This study provides further information about the nucleosomal composition of chromatin on the inactive X chromosome and indicates that a number of H2A variants are non-randomly distributed on the active and inactive X chromosomes. ..
  81. Djuzenova C, Elsner I, Katzer A, Worschech E, Distel L, Flentje M, et al. Radiosensitivity in breast cancer assessed by the histone ?-H2AX and 53BP1 foci. Radiat Oncol. 2013;8:98 pubmed publisher
    High expression of constitutive histone ?-H2AX, a sensitive marker of DNA damage, might be indicative of defective DNA repair pathway or genomic instability...
  82. Tu W, Li B, Huang B, Wang Y, Liu X, Guan H, et al. ?H2AX foci formation in the absence of DNA damage: mitotic H2AX phosphorylation is mediated by the DNA-PKcs/CHK2 pathway. FEBS Lett. 2013;587:3437-43 pubmed publisher
    Phosphorylated H2AX is considered to be a biomarker for DNA double-strand breaks (DSB), but recent evidence suggests that ?H2AX does not always indicate the presence of DSB...