Affinage

Showing H2AX — H2AFX is a alias.

H2AX

Histone H2AX · UniProt P16104

Length
143 aa
Mass
15.1 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

H2AX is a histone H2A variant that functions as the central chromatin sensor of DNA double-strand breaks (DSBs): break formation triggers rapid phosphorylation of its C-terminal Ser139 to generate γ-H2AX, marking large (~2×10^6 bp) chromatin domains around each lesion (PMID:9488723). This phosphorylation is executed primarily by ATM, with DNA-PK acting redundantly to ensure that loss of both kinases is required to eliminate the IR-induced signal (PMID:11571274, PMID:15059890), while VRK1 also directly phosphorylates Ser139 and supports chromatin relaxation after damage (PMID:25923214). γ-H2AX is not needed for the initial recruitment of repair/signaling factors but is required for their stable accumulation and retention in irradiation-induced foci, including NBS1, 53BP1 and BRCA1 (PMID:12792649), and genetic rescue with a Ser-to-Ala/Glu mutant fails to restore genomic stability, establishing Ser139 phosphorylation as functionally essential (PMID:12914701). The mark spreads across chromatin in a manner dictated by topological domain boundaries (PMID:32572033) and acts through the reader MDC1 to direct homologous recombination between sister chromatids (PMID:20703100), to protect coding-end hairpins from CtIP-mediated resection (PMID:21160476), and to recruit FANCD2 at stalled forks within the FA/BRCA pathway (PMID:17304220); in the absence of ATR, ATM/DNA-PK-dependent Ser139 phosphorylation stabilizes collapsed replication forks (PMID:19049966). The signal is reversed by distinct phosphatases acting on different lesion contexts: PP2A at DSBs (PMID:16310392), the PP4C/PP4R2/PP4R3β complex at replication-associated breaks (PMID:18614045), Wip1 to terminate the response (PMID:20460517), and EYA, which dephosphorylates the C-terminal Tyr142 to shift γ-H2AX from apoptotic to repair-factor binding (PMID:19234442). Beyond phosphorylation, H2AX is regulated by an extensive modification network: TIP60-UBC13 acetylation-then-ubiquitination drives H2AX release from chromatin (PMID:17709392), FACT mediates H2AX/H2A nucleosome exchange in a phosphorylation- and PARP1-regulated manner (PMID:18406329), SIRT1 deacetylates Lys5 to permit Ser139 phosphorylation (PMID:35258628), RNF2-BMI1 monoubiquitination at K119/120 and SUV39H2 methylation at K134 promote γ-H2AX formation (PMID:21676867, PMID:25487737), UBE2T-RNF8 monoubiquitination links γ-H2AX to CHK1 activation (PMID:33087136), ADP-ribosylation at Glu141 directs Neil3 recruitment for base excision repair (PMID:33264433), and a PRMT5-RNF168-SMURF2 axis with the deubiquitinase Dub3 governs H2AX proteostasis and repair-factor focus formation (PMID:24704006, PMID:31533041). H2AX activity extends beyond repair to cell-fate decisions, being required for p21-dependent cell-cycle arrest (PMID:19273588), DNA-ladder formation during apoptosis via JNK and CAD (PMID:16818236), and assembly of an AIF/CypA DNA-degrading complex in caspase-independent necroptosis (PMID:22972376). In the germline, H2AX phosphorylation mediates meiotic sex chromosome inactivation downstream of BRCA1/ATR (PMID:15589157), controls meiotic telomere clustering (PMID:14530383), and drives oocyte elimination at asynapsis (PMID:26509888), with MOF-dependent H4K16 acetylation enabling chromatin-wide γ-H2AX spreading in meiosis (PMID:29795555); it is additionally required for hypoxia-driven endothelial proliferation and neovascularization (PMID:19377486).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 1998 High

    Established that DSBs are physically signaled in chromatin by a specific histone modification, defining γ-H2AX as a megabase-scale break marker.

    Evidence 2D gel electrophoresis with 32P incorporation after in vivo irradiation of mammalian cells and mice

    PMID:9488723

    Open questions at the time
    • Did not identify the responsible kinase
    • Did not establish the functional consequence of the modification
  2. 2001 High

    Identified ATM as the major Ser139 kinase with DNA-PK as a backup, answering which signaling kinase couples break detection to the chromatin mark.

    Evidence ATM-/- and DNA-PKcs-/- cells, in vitro kinase assay, reconstitution and wortmannin inhibition

    PMID:11571274

    Open questions at the time
    • Relative contribution of each kinase at different lesion types not fully resolved
    • Did not address replication-stress kinases
  3. 2003 High

    Distinguished initial factor recruitment from stable focus accumulation, showing γ-H2AX is a retention/amplification platform rather than the primary recruitment signal.

    Evidence H2AX-/- cells reconstituted with phosphomutants, immunofluorescence and live imaging; phosphomutant rescue in null mice

    PMID:12792649 PMID:12914701

    Open questions at the time
    • Mechanism by which retained factors execute repair not defined
    • Reader proteins bridging γ-H2AX to factors not yet identified
  4. 2004 High

    Connected γ-H2AX to chromatin remodeling by showing direct recruitment of the INO80 complex, beginning the mechanistic picture of how the mark reshapes chromatin at breaks.

    Evidence Co-IP, ChIP at HO-induced DSB and genetic epistasis in yeast

    PMID:15607974

    Open questions at the time
    • Conservation of the Nhp10-γH2A interaction to mammals not established here
    • Functional outcome of remodeling on repair pathway choice unresolved
  5. 2004 High

    Resolved kinase redundancy by showing combined ATM/DNA-PK loss is required to abolish IR-induced phosphorylation and that DNA-PK contributes to MDC1/53BP1 recruitment.

    Evidence Human fibroblasts/MEFs lacking ATM or DNA-PK, LY294002 inhibition, DT40 double-knockouts

    PMID:15059890

    Open questions at the time
    • Did not address ATR contribution during replication
    • Spatial division of labor between kinases at a single break not mapped
  6. 2005 High

    Identified PP2A as the DSB-associated eraser, establishing that the γ-H2AX signal is actively reversed to permit repair completion.

    Evidence In vitro phosphatase assay, Co-IP, colocalization and RNAi with repair/survival readouts

    PMID:16310392

    Open questions at the time
    • Did not distinguish lesion-context specificity from other phosphatases
    • Regulation of PP2A recruitment timing unresolved
  7. 2003 High

    Showed DNA-PK can be activated by and phosphorylate H2AX within nucleosomes, and that acetylation enhances this only in the nucleosomal context, linking chromatin state to mark deposition.

    Evidence In vitro kinase assays with reconstituted, acetylated/non-acetylated nucleosomes

    PMID:14627815

    Open questions at the time
    • In vivo relevance of acetylation-stimulated phosphorylation not tested here
    • Identity of the acetyltransferase not addressed
  8. 2006 High

    Defined a repair-independent role for γ-H2AX in apoptotic DNA fragmentation, showing it is required for CAD-mediated DNA laddering downstream of JNK.

    Evidence H2AX-/- MEFs, in vitro CAD degradation assay, caspase activity assays

    PMID:16818236

    Open questions at the time
    • How γ-H2AX enables CAD access to DNA not structurally defined
    • Generality across apoptotic stimuli not fully tested
  9. 2006 High

    Showed that in late apoptosis DNA-PK, not ATM (which is degraded), drives γ-H2AX, refining kinase usage by cellular context.

    Evidence ATM-/- and DNA-PKcs-/- cells, kinase inhibition, autophosphorylation immunoblot

    PMID:16567133

    Open questions at the time
    • Trigger for DNA-PK activation in apoptotic chromatin not defined
    • Link to the CAD fragmentation step not mechanistically bridged
  10. 2007 High

    Placed H2AX in the FA/BRCA pathway by showing γ-H2AX is required for BRCA1-dependent FANCD2 recruitment at stalled forks, extending its role to replication stress.

    Evidence H2AX-null cells, phosphomutant, MMC sensitivity, chromatin fractionation and double-depletion epistasis

    PMID:17304220

    Open questions at the time
    • Direct physical γH2AX-FANCD2 contact vs indirect not resolved
    • Reader linking γ-H2AX to FANCD2 not identified
  11. 2007 High

    Established acetylation-coupled ubiquitination by TIP60-UBC13 as the mechanism for H2AX release from damaged chromatin, adding histone dynamics to the response.

    Evidence In vitro acetylation and ubiquitination assays, chromatin fractionation after IR

    PMID:17709392

    Open questions at the time
    • Acetylated lysine residue not specified here
    • Downstream fate of released H2AX not tracked
  12. 2008 High

    Identified the FACT complex as the machine that exchanges H2AX in nucleosomes, with phosphorylation promoting and PARP1-ribosylation inhibiting exchange, defining mark turnover dynamics.

    Evidence Purification of H2AX-associated factors, in vitro nucleosome exchange, DNA-PK and PARP1 activity assays

    PMID:18406329

    Open questions at the time
    • In vivo contribution of FACT exchange to repair outcome not quantified
    • Coordination with INO80 remodeling not addressed
  13. 2008 High

    Defined a replication-specific eraser, the PP4C/PP4R2/PP4R3β complex, distinguishing erasure of ATR-generated γ-H2AX from PP2A action at DSBs.

    Evidence In vitro phosphatase assay on mononucleosomes, RNAi, clonogenic survival with pathway-specific drugs

    PMID:18614045

    Open questions at the time
    • Recruitment mechanism of PP4 to replication foci unresolved
    • Crosstalk with PP2A/Wip1 not mapped
  14. 2008 High

    Demonstrated that H2AX stabilizes collapsed forks in ATR-deficient cells via ATM/DNA-PK Ser139 phosphorylation, integrating H2AX into the replication-stress response.

    Evidence ATR/H2AX double-deficient cells, S139A mutant, cytogenetics, Rad51 immunofluorescence

    PMID:19049966

    Open questions at the time
    • How γ-H2AX promotes Rad51 loading mechanistically unresolved
    • Direct vs indirect fork protection not distinguished
  15. 2009 High

    Revealed a checkpoint role by showing H2AX is required to stabilize p21 and enforce cell-cycle arrest after replication stalling, preventing mitotic catastrophe.

    Evidence H2AX-/- cells and RNAi, AAV-induced stalling, flow cytometry, proteasome rescue, complementation

    PMID:19273588

    Open questions at the time
    • Molecular link from γ-H2AX chromatin to p21 stabilization not defined
    • Role of p53 upstream of p21 in this context not dissected
  16. 2009 High

    Showed ATM and H2AX have complementary essential roles, with H2AX required to repair oxidative damage accumulating in ATM deficiency, explaining their synthetic lethality.

    Evidence ATM/H2AX double-knockout mice and MEFs, genomic instability and embryonic lethality analysis

    PMID:18599436

    Open questions at the time
    • Direct biochemical role of H2AX in oxidative damage repair not defined
    • Pathway connecting H2AX to oxidative lesion repair unresolved
  17. 2009 High

    Uncovered a life/death switch at the C-terminal tail, where EYA dephosphorylation of Tyr142 biases between apoptotic and repair factor binding to γ-H2AX.

    Evidence In vitro phosphatase assay, Y142 mutagenesis, Co-IP, genotoxic stress assays

    PMID:19234442

    Open questions at the time
    • Identity of the Y142 kinase not addressed here
    • Specific apoptotic factors recruited not fully enumerated
  18. 2010 High

    Added Wip1 as a phosphatase that terminates the γ-H2AX response, linking the mark's erasure to oncogenic-stress regulation.

    Evidence In vitro phosphatase assay, ectopic expression and Wip1 deletion, repair foci imaging

    PMID:20460517

    Open questions at the time
    • Lesion-context specificity relative to PP2A/PP4 not defined
    • Recruitment of Wip1 to foci not characterized
  19. 2010 Medium

    Established MDC1-interacting residues of H2AX as the principal determinant of sister-chromatid HR and IR resistance, mapping the reader-dependent output of the mark.

    Evidence Mass spectrometry of IR-treated cells, H2AX residue mutagenesis, HR and clonogenic assays

    PMID:20703100

    Open questions at the time
    • Single-laboratory study without independent replication
    • Functions of additional modified residues only partially defined
  20. 2010 High

    Showed γ-H2AX/MDC1 protects hairpin-sealed coding ends from CtIP resection in G1, defining a role in suppressing aberrant joining and deletions.

    Evidence H2AX-/- lymphocytes, RAG-generated DSBs, CtIP knockdown epistasis, sequencing of joins

    PMID:21160476

    Open questions at the time
    • Direct mechanism by which MDC1 blocks CtIP access not structurally defined
    • Generality beyond V(D)J coding ends not addressed
  21. 2011 High

    Identified RNF2-BMI1 monoubiquitination at K119/120 as a prerequisite for efficient γ-H2AX formation and ATM recruitment, defining an upstream chromatin modification driving the response.

    Evidence K119/120R mutagenesis, RNF2-BMI1 Co-IP, siRNA, foci analysis after IR

    PMID:21676867

    Open questions at the time
    • How K119/120 ubiquitination promotes ATM recruitment mechanistically unresolved
    • Interplay with RNF8/RNF168 ubiquitination not fully integrated
  22. 2012 High

    Extended H2AX into caspase-independent necroptosis by showing γ-H2AX forms an AIF/CypA DNA-degrading complex, with ATM and DNA-PK acting in temporally distinct waves.

    Evidence H2AX-/- cells, S139A/S139E rescue, ATM/DNA-PK genetic and pharmacologic interventions, AIF Co-IP

    PMID:22972376

    Open questions at the time
    • Structural basis of the γH2AX-AIF-CypA complex not defined
    • How nuclear γ-H2AX engages AIF mechanistically unresolved
  23. 2012 Medium

    Proposed a feed-forward role in oxidative stress, with H2AX promoting Nox1/Rac1-driven ROS generation and cell death.

    Evidence H2AX overexpression/knockdown, Nox1 siRNA, Rac1 dominant-negative, ROS measurement, NOXA1/14-3-3ζ Co-IP

    PMID:22237206

    Open questions at the time
    • Single-laboratory study without reconstitution
    • Mechanism by which a chromatin histone modulates cytoplasmic Nox1 unclear
    • Direct vs indirect effect on NOXA1/14-3-3ζ not resolved
  24. 2014 High

    Identified SUV39H2 methylation of K134 as a positive regulator of γ-H2AX formation, adding a methylation layer to mark control with clinical correlation.

    Evidence In vitro methyltransferase assay, K134 mutagenesis, Suv39h2 KO cells, tissue microarray

    PMID:25487737

    Open questions at the time
    • Mechanistic link between K134 methylation and S139 phosphorylation not defined
    • Reader of K134 methylation not identified
  25. 2014 High

    Defined Dub3 as a deubiquitinase counteracting RNF8/RNF168 on H2AX, controlling 53BP1/BRCA1 focus formation and tuning the strength of the response.

    Evidence In vitro deubiquitination assay, Co-IP, RNF8/RNF168 counter-assay, catalytic-dead controls, foci analysis

    PMID:24704006

    Open questions at the time
    • How Dub3 selectively spares MDC1/γH2AX foci not defined
    • Regulation of Dub3 recruitment to damage sites unresolved
  26. 2015 High

    Identified VRK1 as a direct Ser139 kinase that also supports histone acetylation-driven chromatin relaxation, broadening the kinase repertoire for γ-H2AX.

    Evidence In vitro kinase assay on nucleosomes, Co-IP, kinase-dead rescue, immunofluorescence

    PMID:25923214

    Open questions at the time
    • Relative contribution of VRK1 versus ATM/DNA-PK in vivo not quantified
    • Conditions favoring VRK1 usage unresolved
  27. 2015 High

    Demonstrated that γH2AFX on asynapsed chromosomes is a causal mediator of oocyte elimination, establishing a quality-control function in meiosis.

    Evidence H2afx KO and point-mutant mice on XO background, oocyte counting, γH2AFX immunostaining

    PMID:26509888

    Open questions at the time
    • Downstream effectors translating γH2AFX into oocyte death not identified
    • Link to apoptotic machinery in oocytes not defined
  28. 2016 Medium

    Showed chronic oxidative stress destabilizes H2AX via RNF168-mediated polyubiquitination and proteasomal degradation, connecting redox state to H2AX abundance.

    Evidence Co-IP, ubiquitination assays, proteasome rescue, JunD/Nrf2 manipulation in breast cancer models

    PMID:27006338

    Open questions at the time
    • Single-laboratory study
    • How RNF168 switches from a stabilizer to a degrader of H2AX not reconciled with later work
  29. 2018 High

    Defined MOF/H4K16ac as required for chromatin-wide spreading of all three meiotic γH2AX waves, explaining how the mark expands beyond chromosome axes during MSCI.

    Evidence Germ-cell-specific Mof cKO mice, γH2AX and MDC1 immunostaining, RAD51 and crossover analysis

    PMID:29795555

    Open questions at the time
    • Direct biochemical link between H4K16ac and γH2AX spreading not defined
    • Whether MOF acts identically in somatic DSB spreading not tested
  30. 2019 Medium

    Defined a PRMT5-RNF168-SMURF2 cascade balancing H2AX stabilization and degradation, explaining H2AX proteostasis in MTAP-deficient cancer.

    Evidence Knockdown/overexpression of PRMT5/RNF168/SMURF2, Co-IP, ubiquitination assays in glioblastoma models

    PMID:31533041

    Open questions at the time
    • Single-laboratory study
    • Reconciliation of RNF168 as stabilizer here versus degrader elsewhere not addressed
  31. 2020 High

    Discovered ADP-ribosylation at Glu141 as a base-excision-repair-directing mark that recruits Neil3 and prevents erroneous DSB-factor accumulation at BER sites.

    Evidence Mass spectrometry site identification, E141A mutagenesis, Neil3 recruitment assays

    PMID:33264433

    Open questions at the time
    • Enzyme depositing the E141 ADP-ribosylation not identified
    • Crosstalk between E141 ribosylation and S139 phosphorylation only partially defined
  32. 2020 High

    Showed chromosomal topology, not lesion identity, primarily shapes γH2AX domain landscapes, with TAD borders constraining mark spreading.

    Evidence Hi-C combined with γH2AX ChIP-seq at defined DSB sites

    PMID:32572033

    Open questions at the time
    • Functional consequence of asymmetric γH2AX domains for repair not tested
    • Mechanism by which borders block spreading not defined
  33. 2020 Medium

    Identified UBE2T-RNF8 monoubiquitination of H2AX at K119/120 as a driver of CHK1 activation and radioresistance, linking the mark to checkpoint signaling.

    Evidence Co-IP, K119/120R and UBE2T C86A mutants, CHK1 chromatin fractionation, clonogenic survival and xenografts

    PMID:33087136

    Open questions at the time
    • Single-laboratory study
    • Relationship to RNF2-BMI1 monoubiquitination at the same residues not reconciled
  34. 2021 Medium

    Linked H2AX to transcriptional activation, showing HMGA2-induced nicks trigger FACT-mediated H2AX deposition and γH2AX-dependent demethylation at TGFB1-responsive promoters.

    Evidence HMGA2 manipulation, H2AX S139 mutation, FACT assays, DNA methylation and TSS occupancy analysis

    PMID:33594057

    Open questions at the time
    • Single-laboratory study with complex multi-step mechanism
    • Generality beyond TGFB1 target genes not established
  35. 2023 High

    Defined a SIRT1-H2AX axis in which Lys5 deacetylation licenses Ser139 phosphorylation, integrating acetylation control of the mark with apoptotic outcome in cardiomyocytes.

    Evidence Cardiomyocyte-specific Sirt1 cKO mice, SIRT1 manipulation in H9c2 cells, K5Q and S139A mutants, caspase-3 assay

    PMID:35258628

    Open questions at the time
    • Acetyltransferase opposing SIRT1 at K5 not identified here
    • Mechanism by which K5 acetylation blocks S139 phosphorylation not structurally defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense H2AX modification network (phosphorylation, acetylation, ubiquitination, methylation, ADP-ribosylation) is integrated in time and space to specify repair versus death versus checkpoint outcomes at a single lesion remains unresolved.
  • No unified model linking the combinatorial modification code to specific functional outputs
  • Conflicting roles of RNF168 as both stabilizer and degrader of H2AX not reconciled
  • Structural basis for reader discrimination of distinct modified tails undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0042393 histone binding 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-1474165 Reproduction 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
AIFATMDNA-PKEYAFACTMDC1RNF168
Complex memberships
γH2AX-AIF-CypA DNA-degrading complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DNA double-strand breaks (DSBs) induce rapid phosphorylation of histone H2AX specifically at serine 139, generating γ-H2AX; approximately 2×10^6 base pairs of chromatin are involved per DSB, indicating large-scale chromatin modification at each break site. Two-dimensional gel electrophoresis, 32P incorporation, in vivo irradiation of mammalian cells and mice The Journal of biological chemistry High 9488723
2001 ATM is the major kinase responsible for H2AX phosphorylation at serine 139 in response to DSBs in vivo; ATM can phosphorylate H2AX in vitro; DNA-PK contributes residual phosphorylation in ATM-deficient cells, while ATR is not responsible in non-replicating cells. ATM-/- and DNA-PKcs-/- cell lines/MEFs, in vitro kinase assay, ectopic ATM reconstitution, wortmannin inhibition The Journal of biological chemistry High 11571274
2004 ATM and DNA-PK function redundantly to phosphorylate H2AX after ionizing radiation; ablation of both kinases is required to eliminate IR-induced H2AX phosphorylation; ATR is not required for H2AX phosphorylation by DSBs in non-replicating cells; DNA-PK-mediated H2AX phosphorylation contributes to MDC1 and 53BP1 recruitment to DSB sites. Human fibroblasts and MEFs lacking DNA-PK or ATM, LY294002 inhibition, chicken DT40 double-knockout cells Cancer research High 15059890
2003 γ-H2AX is not required for initial recruitment of repair/signaling proteins (Nbs1, 53BP1, Brca1) to DSBs, but is required for their subsequent accumulation and retention into irradiation-induced foci (IRIF); phosphorylation-dead H2AX mutants confirm this distinction. H2AX-/- cells reconstituted with phosphorylation mutants, immunofluorescence, live-cell imaging Nature cell biology High 12792649
2004 The INO80 ATP-dependent chromatin remodeling complex is recruited to DSBs through a direct interaction between the Nhp10 (HMG-like) subunit of INO80 and γ-H2AX (phosphorylated histone H2A in yeast); loss of Nhp10 or γ-H2AX reduces INO80 recruitment; INO80 components show synthetic genetic interactions with the RAD52 repair pathway. Co-immunoprecipitation, chromatin immunoprecipitation at HO endonuclease-induced DSB in yeast, genetic epistasis Cell High 15607974
2005 Protein phosphatase 2A (PP2A) catalytic subunit directly dephosphorylates γ-H2AX in vitro, co-immunoprecipitates and co-localizes with γ-H2AX in DNA damage foci; PP2A recruitment to foci is H2AX-dependent; PP2A inhibition/knockdown causes γ-H2AX foci persistence, inefficient DNA repair, and hypersensitivity to DNA damage. Co-immunoprecipitation, in vitro phosphatase assay, RNAi knockdown, immunofluorescence colocalization Molecular cell High 16310392
2008 A PP4 phosphatase complex (PP4C/PP4R2/PP4R3β) specifically dephosphorylates ATR-mediated γ-H2AX generated during DNA replication, acting directly on γ-H2AX within mononucleosomes in vitro; PP4 silencing causes persistence of replication-associated γ-H2AX foci and hypersensitivity to replication inhibitors but not radiomimetic drugs, indicating pathway specificity distinct from PP2A. In vitro phosphatase assay with mononucleosomes, RNAi knockdown, clonogenic survival, immunofluorescence Molecular cell High 18614045
2009 EYA protein tyrosine phosphatase dephosphorylates a C-terminal tyrosine (Y142) of H2AX in response to genotoxic stress; when Y142 is phosphorylated, pro-apoptotic factors are recruited to the γ-H2AX tail; EYA-mediated dephosphorylation of Y142 shifts the balance toward DNA repair factor recruitment rather than apoptosis. In vitro phosphatase assay, mutation of Y142, co-immunoprecipitation, mammalian cell genotoxic stress assays Nature High 19234442
2007 TIP60 histone acetyltransferase acetylates H2AX following ionizing radiation, which then promotes ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13; this TIP60-UBC13-dependent acetylation-then-ubiquitination is required for H2AX release from damaged chromatin, enhancing histone dynamics during DNA damage response. Ionizing radiation treatment of human cells, in vitro acetylation and ubiquitination assays, immunoprecipitation, chromatin fractionation Molecular and cellular biology High 17709392
2008 FACT complex (Spt16/SSRP1) is an H2AX-associated factor that mediates exchange of H2AX with conventional H2A within nucleosomes; DNA-PK-mediated phosphorylation of H2AX facilitates this exchange by inducing nucleosomal conformational changes; PARP1-mediated poly-ADP-ribosylation of Spt16 inhibits FACT-dependent H2AX exchange. Purification of H2AX-associated factors, in vitro nucleosome exchange assay, DNA-PK and PARP1 activity assays Molecular cell High 18406329
2006 H2AX phosphorylation (γ-H2AX) is required for DNA ladder formation during apoptosis but not for caspase-3 activation; JNK (activated by UVA) phosphorylates H2AX; H2AX phosphorylation is critical for DNA degradation by caspase-activated DNase (CAD) in vitro; H2AX-/- MEFs lack DNA fragmentation despite normal caspase-3/CAD activation. H2AX knockout MEFs, in vitro CAD-mediated DNA degradation assay, immunofluorescence, caspase activity assays Molecular cell High 16818236
2006 DNA-PK is solely responsible for H2AX phosphorylation during apoptotic DNA fragmentation, while ATM is dispensable; DNA-PKcs autophosphorylation at S2056 precedes γ-H2AX induction in apoptosis; ATM is proteolytically degraded before DNA fragmentation, leaving DNA-PK as the predominant kinase in late apoptosis. ATM-/- and DNA-PKcs-/- cell lines, pharmacological kinase inhibition, immunoblotting for autophosphorylation, immunofluorescence in apoptotic vs non-apoptotic nuclei DNA repair High 16567133
2003 DNA-PK can be activated by nucleosomes (via Ku binding to ends of nucleosomal DNA) and phosphorylates H2AX within nucleosomes; histone acetylation enhances H2AX phosphorylation by DNA-PK specifically when H2AX is nucleosome-associated but not in free form. In vitro kinase assay with reconstituted nucleosomes, DNA-PK activation assay, acetylated vs non-acetylated nucleosome substrates Nucleic acids research High 14627815
2003 H2AX is required for the accumulation of Nbs1, 53BP1, Brca1, and other factors into IRIF; loss of a single H2AX allele compromises genomic integrity; restoration with wild-type H2AX rescues genomic stability and radiation resistance, but substitution of the conserved serine phosphorylation site (S→A or S→E) abolishes this rescue, establishing that serine phosphorylation is functionally essential. H2AX heterozygous and homozygous null mice, gene rescue with phosphorylation-site mutants, tumor analysis, cytogenetics Cell High 12914701
2010 Wip1 (wild-type p53-induced phosphatase 1) directly dephosphorylates γ-H2AX in vitro and in vivo; ectopic Wip1 expression prematurely removes γ-H2AX, disrupts repair factor recruitment to damage sites, and delays DNA repair; Wip1 deletion enhances γ-H2AX in cells under oncogenic stress. In vitro phosphatase assay, ectopic expression, Wip1 deletion cells, immunofluorescence of repair foci Cancer research High 20460517
2011 Monoubiquitination of H2AX at Lys119/Lys120 by the RNF2-BMI1 E3 ligase complex is required for efficient γ-H2AX formation and ATM recruitment to DSBs; H2AX K120R mutation (abolishing monoubiquitination) impairs p-ATM recruitment, reduces γ-H2AX and MDC1 accumulation at DSBs, and impairs NBS1 and CHK2 activation; the regulatory effect of RNF2-BMI1 on γ-H2AX is ATM-dependent. Site-directed mutagenesis of H2AX (K119/120R), RNF2-BMI1 Co-IP, siRNA knockdown, immunofluorescence foci analysis, ionizing radiation The Journal of biological chemistry High 21676867
2014 SUV39H2 histone methyltransferase methylates H2AX on lysine 134; mutation of K134 significantly reduces γ-H2AX levels; Suv39h2 knockout or knockdown reduces γ-H2AX after DSB induction; K134 methylation positively correlates with γ-H2AX levels in clinical tissue samples. In vitro methyltransferase assay, H2AX K134 mutagenesis, Suv39h2 KO cells, tissue microarray, clonogenic survival Nature communications High 25487737
2004 BRCA1 is required to recruit ATR to XY chromatin at the onset of meiotic sex chromosome inactivation (MSCI); ATR then phosphorylates H2AX on the sex chromosomes; in BRCA1-mutant pachytene cells, ATR mislocalizes and phosphorylates H2AX at aberrant autossomal sites, causing MSCI failure; rare cells where ATR correctly localizes to XY chromatin show H2AX phosphorylation and successful MSCI. Immunofluorescence colocalization in spermatocytes from BRCA1-mutant mice, co-staining of ATR and γH2AX Current biology : CB High 15589157
2007 Phosphorylated H2AX (γH2AX) is required for FANCD2 recruitment to chromatin at stalled replication forks; FANCD2 binding to γH2AX is BRCA1-dependent; H2AX-deficient cells display an FA-like phenotype including excess chromatid-type aberrations and MMC hypersensitivity; this hypersensitivity is not increased by additional FANCD2 depletion, placing H2AX and FANCD2 in the same pathway. H2AX knockout mouse cells, non-phosphorylable H2AX mutant (S136A/S139A), MMC sensitivity, chromatin fractionation, immunofluorescence, genetic epistasis by double depletion The EMBO journal High 17304220
2009 ATM and H2AX have complementary functions; combined ATM/H2AX deficiency causes embryonic lethality and dramatic genomic instability; severe instability in double-deficient cells is associated with a requirement for H2AX in repairing oxidative DNA damage that accumulates due to ATM deficiency. ATM/H2AX double-knockout mice and MEFs, genomic instability assays, embryonic lethality analysis Proceedings of the National Academy of Sciences of the United States of America High 18599436
2008 H2AX is required for endothelial cell proliferation under hypoxic conditions; hypoxia induces replication-associated γ-H2AX in endothelial cells; H2AX deficiency reduces hypoxia-driven neovascularization in pathologic proliferative retinopathy, hind-limb ischemia, and tumor angiogenesis; endothelial-specific H2afx deletion recapitulates this phenotype. H2afx-/- mice, endothelial-specific conditional knockout, in vitro hypoxic cell proliferation assays, retinal neovascularization and tumor angiogenesis models Nature medicine High 19377486
2009 H2AX is required for p21-dependent cell cycle arrest after replication stalling; in H2AX-deficient cells, p21 undergoes proteasome-dependent degradation after stalled replication, leading to mitotic catastrophe; H2AX-proficient cells increase p21 levels and arrest the cell cycle; this establishes H2AX as a component of the p53/p21 cell cycle checkpoint pathway. H2AX-/- cells and RNAi knockdown, AAV-induced stalled replication, flow cytometry, proteasome inhibitor rescue, H2AX complementation Molecular and cellular biology High 19273588
2010 H2AX prevents CtIP-mediated DNA end resection of hairpin-sealed coding ends in G1-phase lymphocytes; γ-H2AX and its reader MDC1 inhibit CtIP access; ATM activates antagonistic pathways modulating this resection; in H2AX-deficient cells, CtIP promotes aberrant hairpin opening, leading to microhomology-mediated joins and chromosomal deletions. H2AX-/- murine lymphocytes, RAG endonuclease-generated DSB analysis, CtIP knockdown epistasis, sequencing of joins, chromosomal deletion analysis Nature High 21160476
2012 H2AX increases ROS generation after DNA damage through the Nox1/Rac1 pathway; H2AX overexpression alone induces ROS; H2AX reduces interaction between Nox1 activator NOXA1 and its inhibitor 14-3-3ζ, thereby increasing Nox1 activity; Nox1 knockdown or Rac1N17 expression reduces H2AX-mediated ROS and cell death. H2AX overexpression/knockdown, Nox1/Nox4 siRNA, Rac1 dominant-negative expression, ROS measurement, co-immunoprecipitation of NOXA1/14-3-3ζ Cell death & disease Medium 22237206
2012 In MNNG-induced caspase-independent necroptosis, ATM and DNA-PK phosphorylate H2AX at S139 in a synergistic but temporally distinct manner (ATM early, DNA-PK later); γH2AX associates with AIF and CypA to form a DNA-degrading complex; H2AX S139A mutation or H2AX ablation abolishes chromatinolysis and necroptosis; phosphomimetic H2AX S139E rescues necroptosis in H2AX-/- cells. H2AX-/- cells, S139A/S139E mutant reconstitution, ATM/DNA-PK knockout and pharmacological inhibition, AIF co-immunoprecipitation Cell death & disease High 22972376
2014 Dub3 ubiquitin hydrolase deubiquitinates H2AX; Dub3 directly interacts with H2AX and deubiquitinates it in vitro; Dub3 overexpression decreases DSB-induced H2AX monoubiquitination and abrogates 53BP1 and BRCA1 focus formation (but not MDC1/γH2AX foci); Dub3 counteracts RNF8 and RNF168 E3 ligases; Dub3 depletion accelerates H2AX dephosphorylation at later time points. In vitro deubiquitination assay, Co-immunoprecipitation, RNF8/RNF168 counter-assay, immunofluorescence foci analysis, catalytic dead mutant Molecular oncology High 24704006
2016 Chronic oxidative stress reduces H2AX protein levels via enhanced interaction with E3 ubiquitin ligase RNF168, leading to H2AX poly-ubiquitination and proteasomal degradation; deficient JunD/Nrf2 antioxidant response drives ROS accumulation and H2AX destabilization. Co-immunoprecipitation of H2AX and RNF168, ubiquitination assays, proteasome inhibitor rescue, JunD/Nrf2 manipulation, breast cancer cell lines and patient samples EMBO molecular medicine Medium 27006338
2019 PRMT5 sustains RNF168 expression, which stabilizes H2AX protein; in the absence of RNF168 (due to PRMT5 suppression in MTAP-deficient cells), the E3 ubiquitin ligase SMURF2 destabilizes H2AX; RNF168 and SMURF2 dynamically interact with H2AX acting as stabilizer and destabilizer respectively, defining a PRMT5-RNF168-SMURF2 cascade controlling H2AX proteostasis. PRMT5/RNF168/SMURF2 knockdown and overexpression, Co-IP, ubiquitination assays, MTAP-deficient glioblastoma cell models Cell reports Medium 31533041
2020 H2AX glutamate 141 (E141) is ADP-ribosylated following oxidative DNA damage; this modification mediates recruitment of Neil3 glycosylase to DNA damage sites for base excision repair (BER); ADP-ribosylation-deficient H2AX E141A mutant enhances γH2AX (S139 phosphorylation) and erroneously accumulates DSB response factors at BER sites. Unbiased mass spectrometry identification of ADP-ribosylation site, E141A mutagenesis, Neil3 recruitment assays, comparison of BER vs DSB response factors The EMBO journal High 33264433
2023 SIRT1 deacetylates H2AX at Lys5, and this deacetylation is required for efficient Ser139 phosphorylation of H2AX; SIRT1 knockdown increases acetyl-Lys5-H2AX and blunts γ-H2AX formation; H2AX K5Q (acetylation mimic) mutant shows reduced Ser139 phosphorylation in response to doxorubicin; K5Q and S139A mutants both enhance caspase-3 activation, demonstrating functional consequence of SIRT1-H2AX axis. Cardiomyocyte-specific Sirt1 conditional knockout mice, SIRT1 knockdown/overexpression in H9c2 cells, K5Q mutant H2AX, immunostaining for acetyl-K5 and phospho-S139 H2AX, caspase-3 assay Cardiovascular research High 35258628
2015 H2AX controls double-strand break repair by homologous recombination (HR) between sister chromatids through interaction of γ-H2AX with the chromatin-associated adaptor protein MDC1; mass spectrometry identified novel IR-responsive post-translationally modified residues of H2AX beyond S139; HR and IR-resistance functions of H2AX are controlled largely by MDC1-interacting residues, with additional H2AX residues modulating these functions. Mass spectrometry of IR-treated cells, mutagenesis of H2AX residues, HR assay (sister chromatid recombination), clonogenic survival Cell cycle (Georgetown, Tex.) Medium 20703100
2008 ATR deficiency leads to H2AX phosphorylation by ATM and DNA-PKcs at collapsed replication forks; increased Rad51 focal accumulation in ATR-deficient cells is largely H2AX-dependent; dual deficiency of ATR and H2AX causes synergistic increases in chromatid breaks; H2AX S139 (the ATM/DNA-PK phosphorylation site) is required for genome stabilization in the absence of ATR. ATR-deficient and H2AX-deficient cells, S139A H2AX mutant, cytogenetic analysis, Rad51 immunofluorescence, genetic double-deficiency The Journal of biological chemistry High 19049966
2005 ATM-dependent H2AX phosphorylation occurs during mitosis in normally growing mammalian cells independently of exogenous DNA damage; two distinct γ-H2AX focal populations exist in unirradiated cells: large amorphous foci colocalizing with DSB repair proteins and smaller foci that do not recruit DSB repair factors; the mitotic γ-H2AX phosphorylation may contribute to fidelity of mitosis independent of DNA damage. Quantitative in situ immunofluorescence, cell cycle analysis, ATM-inhibitor treatment, multiple unirradiated mammalian cell lines Molecular biology of the cell Medium 16030261
2020 Chromosomal contacts (topological structure) of a DSB site are the primary determinants of γH2AX domain landscapes; DSBs that disrupt a topological border allow γH2AX extension into both adjacent compartments; DSBs near a border produce highly asymmetric γH2AX domains with γH2AX nearly absent from one broken end. Hi-C chromosome conformation capture combined with γH2AX ChIP-seq at specific DSB sites Nature communications High 32572033
2015 VRK1 kinase directly phosphorylates H2AX at Ser139 in response to ionizing radiation; VRK1 stably interacts with H2AX and H3 under basal conditions; VRK1 depletion prevents γH2AX foci formation and reduces H3/H4 acetylation required for chromatin relaxation after DNA damage; kinase-active but not kinase-dead VRK1 rescues γH2AX foci formation. In vitro kinase assay with nucleosomal substrate, co-immunoprecipitation, VRK1 depletion/rescue with kinase-dead mutant, immunofluorescence Epigenetics High 25923214
2003 H2AX regulates telomere clustering during meiotic prophase I; H2AX is dispensable for mitotic telomere maintenance and for chromosome fusions from critically shortened or deprotected telomeres; H2AX is required downstream of ATM for proper topological distribution of telomeres during meiosis. H2AX-/- mice, meiotic spread immunofluorescence, telomere FISH, ATM inhibitor treatment The Journal of cell biology Medium 14530383
2021 HMGA2 induces DNA nicks at transcription start sites, which triggers FACT complex to incorporate H2AX-containing nucleosomes; phosphorylation of H2AX at S139 (γH2AX) is then required for repair-mediated DNA demethylation and transcription activation in the context of TGFB1 signaling. HMGA2 manipulation, H2AX S139 mutation, FACT complex assays, DNA methylation analysis, transcription start site occupancy Nature communications Medium 33594057
2015 Phosphorylated H2AFX (γH2AFX) on asynapsed chromosomes during meiotic prophase I triggers oocyte elimination at diplonema in mice with chromosome abnormalities (XO and translocations); deletion or point mutation of H2afx restores oocyte numbers in XO females to wild-type (XX) levels, establishing γH2AFX as a causal mediator of oocyte elimination. H2afx knockout and point mutant mice (XO background), oocyte counting, γH2AFX immunostaining, chromosomal asynapsis analysis PLoS genetics High 26509888
2018 MOF histone acetyltransferase (which generates H4K16ac) is required for the chromatin-wide expansion of all three waves of H2AX phosphorylation during male meiotic prophase I; without MOF, γH2AX signals are restricted to chromosomal axes and fail to expand to broad chromatin domains; MSCI fails in ~40% of Mof cKO pachytene cells; MOF facilitates meiotic DSB repair after RAD51 recruitment. Germ cell-specific Mof conditional knockout mice (Stra8-Cre), γH2AX immunostaining, MDC1 colocalization, RAD51 recruitment assay, crossover analysis PLoS genetics High 29795555
2020 UBE2T-RNF8 acts as an E2-E3 pair that monoubiquitinates H2AX/γH2AX at K119/K120 upon radiation exposure; this monoubiquitination facilitates CHK1 phosphorylation/activation and promotes CHK1 release from chromatin; mutations in UBE2T (C86A, E2-dead) or H2AX (K119/120R) abolish CHK1 activation; CHK1 inhibition impairs UBE2T-mediated radioresistance. Co-IP of UBE2T with H2AX, K119/120R H2AX mutant, C86A UBE2T mutant, CHK1 chromatin fractionation, clonogenic survival, xenograft models Journal of experimental & clinical cancer research : CR Medium 33087136

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. The Journal of biological chemistry 4420 9488723
2001 ATM phosphorylates histone H2AX in response to DNA double-strand breaks. The Journal of biological chemistry 1580 11571274
2008 Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In vivo (Athens, Greece) 1072 18610740
2008 Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic acids research 1028 18772227
2004 ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer research 827 15059890
2004 H2AX: the histone guardian of the genome. DNA repair 820 15279782
2003 Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nature cell biology 809 12792649
2002 Histone H2A variants H2AX and H2AZ. Current opinion in genetics & development 592 11893489
2012 Histone H2AX phosphorylation: a marker for DNA damage. Methods in molecular biology (Clifton, N.J.) 570 22941631
2010 H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. Journal of nucleic acids 481 20811597
2003 H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 465 12914701
2005 gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Molecular cell 451 16310392
2004 INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell 449 15607974
2009 Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature 439 19234442
2003 Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 404 12914700
2003 Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochemistry and cell biology = Biochimie et biologie cellulaire 367 12897845
2004 BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation. Current biology : CB 326 15589157
2006 Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Molecular cell 312 16818236
2007 DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. Molecular and cellular biology 297 17709392
2015 Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions. Nucleic acids research 289 25712102
2003 Expression of phosphorylated histone H2AX in cultured cell lines following exposure to X-rays. International journal of radiation biology 277 12943243
2009 H2AX: functional roles and potential applications. Chromosoma 265 19707781
2012 DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway. Cell death & disease 250 22237206
2004 Phosphorylation of histone H2AX as a measure of radiosensitivity. International journal of radiation oncology, biology, physics 246 14751500
2010 Focus on histone variant H2AX: to be or not to be. FEBS letters 243 20493860
2003 Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy. The Journal of biological chemistry 241 14561744
2008 Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature 233 18185516
2006 H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Molecular cell 232 16427010
2005 ATM-dependent DNA damage-independent mitotic phosphorylation of H2AX in normally growing mammalian cells. Molecular biology of the cell 223 16030261
2008 FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16. Molecular cell 204 18406329
2008 A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Molecular cell 201 18614045
2004 H2AX may function as an anchor to hold broken chromosomal DNA ends in close proximity. Cell cycle (Georgetown, Tex.) 196 14712078
2007 Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents. Cytometry. Part A : the journal of the International Society for Analytical Cytology 178 17622968
2006 DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. DNA repair 175 16567133
2006 Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants. Cell cycle (Georgetown, Tex.) 175 16940754
2003 DNA double-strand breaks and gamma-H2AX signaling in the testis. Biology of reproduction 175 12533428
2020 DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner. Nature communications 173 32572033
2009 gamma-H2AX as protein biomarker for radiation exposure. Annali dell'Istituto superiore di sanita 166 19861731
2006 Induction and quantification of gamma-H2AX foci following low and high LET-irradiation. International journal of radiation biology 166 16546909
2005 DNA repair: the importance of phosphorylating histone H2AX. Current biology : CB 164 15694301
2009 H2AX is required for cell cycle arrest via the p53/p21 pathway. Molecular and cellular biology 144 19273588
2011 Monoubiquitination of H2AX protein regulates DNA damage response signaling. The Journal of biological chemistry 143 21676867
2016 Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients. EMBO molecular medicine 137 27006338
2010 Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response. Cancer research 129 20460517
2010 The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks. Cell cycle (Georgetown, Tex.) 126 20046100
2003 DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner. Nucleic acids research 126 14627815
2009 Kinetics of H2AX phosphorylation after exposure to cisplatin. Cytometry. Part B, Clinical cytometry 125 18727058
2011 MicroRNA-138 modulates DNA damage response by repressing histone H2AX expression. Molecular cancer research : MCR 122 21693595
2009 H2AX phosphorylation as a genotoxicity endpoint. Mutation research 122 19628053
2010 H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes. Nature 120 21160476
2024 H2AX: A key player in DNA damage response and a promising target for cancer therapy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 117 38688170
2011 H2AX phosphorylation at the sites of DNA double-strand breaks in cultivated mammalian cells and tissues. Clinical epigenetics 113 22704343
2009 Histone H2AX is integral to hypoxia-driven neovascularization. Nature medicine 113 19377486
2008 ATR and H2AX cooperate in maintaining genome stability under replication stress. The Journal of biological chemistry 109 19049966
2007 Histone H2AX and Fanconi anemia FANCD2 function in the same pathway to maintain chromosome stability. The EMBO journal 108 17304220
2008 Complementary functions of ATM and H2AX in development and suppression of genomic instability. Proceedings of the National Academy of Sciences of the United States of America 99 18599436
2013 Clustered DNA damage induces pan-nuclear H2AX phosphorylation mediated by ATM and DNA-PK. Nucleic acids research 98 23620287
2014 The nuclear γ-H2AX apoptotic ring: implications for cancers and autoimmune diseases. Cellular and molecular life sciences : CMLS 93 24448903
2014 Critical role of lysine 134 methylation on histone H2AX for γ-H2AX production and DNA repair. Nature communications 92 25487737
2006 H2AX chromatin structures and their response to DNA damage revealed by 4Pi microscopy. Proceedings of the National Academy of Sciences of the United States of America 91 17110439
2020 UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation. Journal of experimental & clinical cancer research : CR 87 33087136
2009 MRE11-RAD50-NBS1 complex dictates DNA repair independent of H2AX. The Journal of biological chemistry 84 19910469
2012 γ-H2AX and other histone post-translational modifications in the clinic. Biochimica et biophysica acta 83 22430255
2012 AIF-mediated caspase-independent necroptosis requires ATM and DNA-PK-induced histone H2AX Ser139 phosphorylation. Cell death & disease 77 22972376
2010 Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis. Cell cycle (Georgetown, Tex.) 74 20697198
2008 Role of H2AX in DNA damage response and human cancers. Mutation research 74 18804552
2011 miR-24-2 controls H2AFX expression regardless of gene copy number alteration and induces apoptosis by targeting antiapoptotic gene BCL-2: a potential for therapeutic intervention. Breast cancer research : BCR 73 21463514
2011 γ-H2AX detection in peripheral blood lymphocytes, splenocytes, bone marrow, xenografts, and skin. Methods in molecular biology (Clifton, N.J.) 67 21057933
2014 γ-H2AX as a biomarker for DNA double-strand breaks in ecotoxicology. Ecotoxicology and environmental safety 66 24780228
2006 gamma-H2AX as a therapeutic target for improving the efficacy of radiation therapy. Current cancer drug targets 66 16712457
2023 SIRT1 in the cardiomyocyte counteracts doxorubicin-induced cardiotoxicity via regulating histone H2AX. Cardiovascular research 64 35258628
2020 Potential application of γ-H2AX as a biodosimetry tool for radiation triage. Mutation research. Reviews in mutation research 61 34083048
2015 Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals. PLoS genetics 60 26509888
2015 VRK1 chromatin kinase phosphorylates H2AX and is required for foci formation induced by DNA damage. Epigenetics 57 25923214
2015 Complementarity of phosphorylated histones H2AX and H3 quantification in different cell lines for genotoxicity screening. Archives of toxicology 53 26404763
2010 Structure and function of histone H2AX. Sub-cellular biochemistry 50 20012577
2003 H2AX regulates meiotic telomere clustering. The Journal of cell biology 50 14530383
2010 H2AX post-translational modifications in the ionizing radiation response and homologous recombination. Cell cycle (Georgetown, Tex.) 49 20703100
2009 Mechanism of elimination of phosphorylated histone H2AX from chromatin after repair of DNA double-strand breaks. Mutation research 49 19682466
2009 Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination. The Journal of experimental medicine 46 19887394
2021 Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation. Nature communications 45 33594057
2019 MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance. Nature communications 45 31729360
2020 ADP-ribosylation of histone variant H2AX promotes base excision repair. The EMBO journal 44 33264433
2014 Gamma histone 2AX (γ-H2AX)as a predictive tool in radiation oncology. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 44 24611829
2013 DNA damage sensor γ -H2AX is increased in preneoplastic lesions of hepatocellular carcinoma. TheScientificWorldJournal 44 23533353
2010 Conserved gammaherpesvirus kinase and histone variant H2AX facilitate gammaherpesvirus latency in vivo. Virology 42 20557919
2018 Monoubiquitinated γ-H2AX: Abundant product and specific biomarker for non-apoptotic DNA double-strand breaks. Toxicology and applied pharmacology 41 30006243
2008 Oxidative stress induces cell cycle-dependent Mre11 recruitment, ATM and Chk2 activation and histone H2AX phosphorylation. Cell cycle (Georgetown, Tex.) 40 18418078
2019 A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis. Cell reports 37 31533041
2015 Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy. Radiation research 37 25844946
2021 The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age. Molecules (Basel, Switzerland) 36 34885784
2015 γ-H2AX promotes hepatocellular carcinoma angiogenesis via EGFR/HIF-1α/VEGF pathways under hypoxic condition. Oncotarget 36 25537504
2014 Dub3 controls DNA damage signalling by direct deubiquitination of H2AX. Molecular oncology 36 24704006
2008 Soluble histone H2AX is induced by DNA replication stress and sensitizes cells to undergo apoptosis. Molecular cancer 36 18616816
2007 Genetic variation in H2AFX contributes to risk of non-Hodgkin lymphoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 36 17548670
2005 H2AX: tailoring histone H2A for chromatin-dependent genomic integrity. Biochemistry and cell biology = Biochimie et biologie cellulaire 36 16094454
2003 Expression and radiation-induced phosphorylation of histone H2AX in mammalian cells. Journal of radiation research 36 12841599
2021 Detection and quantification of γ-H2AX using a dissociation enhanced lanthanide fluorescence immunoassay. Scientific reports 34 33903655
2018 MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. PLoS genetics 34 29795555
2013 H2AX a promising biomarker for lung cancer: a review. Cancer investigation 34 24164298

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