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Formation of Dynamic γ-H2AX Domains along Broken DNA Strands Is Distinctly Regulated by ATM and MDC1 and Dependent upon H2AX Densities in Chromatin
Open accessAbstract
A hallmark of the cellular response to DNA double-strand breaks (DSBs) is histone H2AX phosphorylation in chromatin to generate gamma-H2AX. Here, we demonstrate that gamma-H2AX densities increase transiently along DNA strands as they are broken and repaired in G1 phase cells. The region across which gamma-H2AX forms does not spread as DSBs persist; rather, gamma-H2AX densities equilibrate at distinct levels within a fixed distance from DNA ends. Although both ATM and DNA-PKcs generate gamma-H2AX, only ATM promotes gamma-H2AX formation to maximal distance and maintains gamma-H2AX densities. MDC1 is essential for gamma-H2AX formation at high densities near DSBs, but not for generation of gamma-H2AX over distal sequences. Reduced H2AX levels in chromatin impair the density, but not the distance, of gamma-H2AX formed. Our data suggest that H2AX fuels a gamma-H2AX self-reinforcing mechanism that retains MDC1 and activated ATM in chromatin near DSBs and promotes continued local phosphorylation of H2AX.
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“ATR and ATM also phosphorylate histone H2AX at Ser-139 (γH2AX) in response to DNA double-strand breaks (DSBs), which spreads along the DNA up to 200–400 kb and helps in the recruitment of proteins involved in DNA damage repair and checkpoint activation [29].”
From ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle (2016) · cites this paper as [29]
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“Additionally, it is well established that ATR and ATM allow H2AX phosphorylation and spreading at the damage site, which changes the chromatin structure near the damage site and executes DNA repair through the HR pathway [21-23, 26, 63].”
From NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites (2013) · cites this paper as [21]
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Cites
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438
RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Shinkai, Y. (1992) · Cell · doi:10.1016/0092-8674(92)90029-c · Cited by 2,651
Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo
Rogakou, E. P., Boon, C., Redon, C., & Bonner, W. M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.5.905 · Cited by 2,422
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., & Bonner, W. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00610-2 · Cited by 2,098
ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., & Chen, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100466200 · Cited by 1,954
Genomic Instability in Mice Lacking Histone H2AX
Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., Reina-San-Martin, B., Coppola, V., Meffre, E., Difilippantonio, M. J., et al. (2002) · Science · doi:10.1126/science.1069398 · Cited by 1,385
-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin
Kinner, A., Wu, W., Staudt, C., & Iliakis, G. E. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn550 · Cited by 1,303
A Critical Role for Dnmt1 and DNA Methylation in T Cell Development, Function, and Survival
Lee, P. P., Fitzpatrick, D. R., Beard, C., Jessup, H. K., Lehar, S. M., Makar, K. W., Pérez‐Melgosa, M., Sweetser, M. T., Schlissel, M. S., Nguyen, S., et al. (2001) · Immunity · doi:10.1016/s1074-7613(01)00227-8 · Cited by 1,282
Hickson, I., Zhao, Y., Richardson, C. J., Green, S. J., Martin, N. M. B., Orr, A. I., Reaper, P. M., Jackson, S. P., Curtin, N. J., & Smith, G. C. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2727 · Cited by 1,220
RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins
Mailand, N., Bekker‐Jensen, S., Kildegaard, H. F., Melander, F., Bártek, J., Lukas, C., & Lukas, J. (2007) · Cell · doi:10.1016/j.cell.2007.09.040 · Cited by 1,193
Ma, Y., Pannicke, U., Schwarz, K., & Lieber, M. R. (2002) · Cell · doi:10.1016/s0092-8674(02)00671-2 · Cited by 1,166
Stucki, M., Clapperton, J. A., Mohammad, D. H., Yaffe, M. B., Smerdon, S. J., & Jackson, S. P. (2005) · Cell · doi:10.1016/j.cell.2005.09.038 · Cited by 1,164
RNF8 Transduces the DNA-Damage Signal via Histone Ubiquitylation and Checkpoint Protein Assembly
Huen, M. S. Y., Grant, R. A., Manke, I. A., Minn, K. T., Yu, X., Yaffe, M. B., & Chen, J. (2007) · Cell · doi:10.1016/j.cell.2007.09.041 · Cited by 1,068
ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation
Stiff, T., O’Driscoll, M., Rief, N., Iwabuchi, K., Löbrich, M., & Jeggo, P. A. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3207 · Cited by 1,050
Jonkers, J., Meuwissen, R. L. J., van der Gulden, H. M. L., Peterse, H. L., van der Valk, M., & Berns, A. J. M. (2001) · Nature Genetics · doi:10.1038/ng747 · Cited by 1,044
The Mechanism and Regulation of Chromosomal V(D)J Recombination
Bassing, C. H., Swat, W., & Alt, F. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00675-x · Cited by 1,006
Self-citationHistone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks
Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., Bonner, R. F., Bonner, W. M., & Nussenzweig, A. (2003) · Nature Cell Biology · doi:10.1038/ncb1004 · Cited by 989
MDC1 is a mediator of the mammalian DNA damage checkpoint
Stewart, G. S., Wang, B., Bignell, C. R., Taylor, A. M. R., & Elledge, S. J. (2003) · Nature · doi:10.1038/nature01446 · Cited by 874
Acetylation by Tip60 Is Required for Selective Histone Variant Exchange at DNA Lesions
Kusch, T., Florens, L. A., McDonald, W. H., Swanson, S. K., Glaser, R. L., Yates, J. R., Abmayr, S. M., Washburn, M. P., & Workman, J. L. (2004) · Science · doi:10.1126/science.1103455 · Cited by 669
Lou, Z., Minter‐Dykhouse, K., Franco, S., Gostissa, M., Rivera, M. A., Celeste, A., Manis, J. P., van Deursen, J., Nussenzweig, A., Paull, T. T., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2005.11.025 · Cited by 668
DNA damage-induced G2–M checkpoint activation by histone H2AX and 53BP1
Fernández-Capetillo, Ó., Chen, H. T., Celeste, A., Ward, I. M., Romanienko, P. J., Morales, J. C., Naka, K., Xia, Z., Camerini‐Otero, R. D., Motoyama, N., et al. (2002) · Nature Cell Biology · doi:10.1038/ncb884 · Cited by 657
A role for Saccharomyces cerevisiae histone H2A in DNA repair
Downs, J. A., Lowndes, N. F., & Jackson, S. P. (2000) · Nature · doi:10.1038/35050000 · Cited by 650
Ünal, E., Arbel‐Eden, A., Sattler, U., Shroff, R., Lichten, M., Haber, J. E., & Koshland, D. E. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.11.027 · Cited by 589
γ-H2AX Dephosphorylation by Protein Phosphatase 2A Facilitates DNA Double-Strand Break Repair
Chowdhury, D., Keogh, M., Ishii, H., Peterson, C. L., Buratowski, S., & Lieberman, J. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.003 · Cited by 563
H2AX Haploinsufficiency Modifies Genomic Stability and Tumor Susceptibility
Celeste, A., Difilippantonio, S., Difilippantonio, M. J., Fernández-Capetillo, Ó., Pilch, D. R., Sedelnikova, O. A., Eckhaus, M., Ried, T., Bonner, W. M., & Nussenzweig, A. (2003) · Cell · doi:10.1016/s0092-8674(03)00567-1 · Cited by 558
Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX
Bassing, C. H., Chua, K. F., Sekiguchi, J., Suh, H., Whitlow, S. R., Fleming, J. C., Monroe, B., Ciccone, D. N., Yan, C. T., Vlasáková, K., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122228699 · Cited by 537
Self-citationMonoclonal mice generated by nuclear transfer from mature B and T donor cells
Hochedlinger, K., & Jaenisch, R. (2002) · Nature · doi:10.1038/nature718 · Cited by 536
Distribution and Dynamics of Chromatin Modification Induced by a Defined DNA Double-Strand Break
Shroff, R., Arbel‐Eden, A., Pilch, D. R., Ira, G., Bonner, W. M., Petrini, J. H. J., Haber, J. E., & Lichten, M. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.047 · Cited by 524
Bassing, C. H., Suh, H., Ferguson, D. O., Chua, K. F., Manis, J. P., Eckersdorff, M., Gleason, M., Bronson, R. T., Lee, C., & Alt, F. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00566-x · Cited by 497
Self-citationATM stabilizes DNA double-strand-break complexes during V(D)J recombination
Bredemeyer, A. L., Sharma, G. G., Huang, C., Helmink, B. A., Walker, L. M., Khor, K. C., Nuskey, B., Sullivan, K. E., Pandita, T. K., Bassing, C. H., et al. (2006) · Nature · doi:10.1038/nature04866 · Cited by 435
Self-citationγH2AX and MDC1: Anchoring the DNA-damage-response machinery to broken chromosomes
Stucki, M., & Jackson, S. P. (2006) · DNA Repair · doi:10.1016/j.dnarep.2006.01.012 · Cited by 412
DNA Damage-Dependent Acetylation and Ubiquitination of H2AX Enhances Chromatin Dynamics
Ikura, T., Tashiro, S., Kakino, A., Shima, H., Jacob, N. K., Amunugama, R., Yoder, K. E., Izumi, S., Kuraoka, I., Tanaka, K., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00579-07 · Cited by 387
Role of genomic instability and p53 in AID-induced c-myc–Igh translocations
Ramiro, A. R., Janković, M., Callén, E., Difilippantonio, S., Chen, H.-T., McBride, K. M., Eisenreich, T., Chen, J., Dickins, R. A., Lowe, S. W., et al. (2006) · Nature · doi:10.1038/nature04495 · Cited by 346
Response to RAG-Mediated V(D)J Cleavage by NBS1 and γ-H2AX
Chen, H. T., Bhandoola, A., Difilippantonio, M. J., Zhu, J., Brown, M. J., Tai, X., Rogakou, E. P., Brotz, T. M., Bonner, W. M., Ried, T., et al. (2000) · Science · doi:10.1126/science.290.5498.1962 · Cited by 326
H2AX Prevents DNA Breaks from Progressing to Chromosome Breaks and Translocations
Franco, S., Gostissa, M., Zha, S., Lombard, D. B., Murphy, M. M., Zarrin, A. A., Yan, C., Tepsuporn, S., Morales, J. C., Adams, M. M., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.005 · Cited by 282
Self-citationLeaky Scid Phenotype Associated with Defective V(D)J Coding End Processing in Artemis-Deficient Mice
Rooney, S., Sekiguchi, J., Zhu, C., Cheng, H.-L., Manis, J. P., Whitlow, S. R., DeVido, J., Foy, D., Chaudhuri, J., Lombard, D. B., et al. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00755-4 · Cited by 278
Nuclear Retention of ATM at Sites of DNA Double Strand Breaks
Andegeko, Y., Moyal, L., Rotman, G., Shiloh, Y., Mittelman, L., & Tsarfaty, I. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102986200 · Cited by 276
V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors.Preprint
Guidos, C. J., Williams, C. J., Grandal, I., Knowles, G. C., Huang, M. T. F., & Danska, J. S. (1996) · Genes & Development · doi:10.1101/gad.10.16.2038 · Cited by 276
Heo, K., Kim, H., Choi, S. H., Choi, J., Kim, K., Gu, J., Lieber, M. R., Yang, A. S., & An, W. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.02.029 · Cited by 263
A PP4-Phosphatase Complex Dephosphorylates γ-H2AX Generated during DNA Replication
Chowdhury, D., Xu, X., Zhong, X., Ahmed, F., Zhong, J., Liao, J., Dykxhoorn, D. M., Weinstock, D. M., Pfeifer, G. P., & Lieberman, J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.05.016 · Cited by 256
HIF-1: A Target For Cancer, Ischemia and Inflammation—Too Good to be True?
Melillo, G. (2004) · Cell Cycle · doi:10.4161/cc.3.2.689 · Cited by 247
Control of Sister Chromatid Recombination by Histone H2AX
Xie, A., Puget, N., Shim, I., Odate, S., Jarzyna, I., Bassing, C. H., Alt, F. W., & Scully, R. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.12.007 · Cited by 211
Self-citationH2AX May Function as an Anchor to Hold Broken Chromosomal DNA Ends in Close Proximity
Bassing, C. H., & Alt, F. W. (2004) · Cell Cycle · doi:10.4161/cc.3.2.684 · Cited by 177
Self-citationMuljo, S. A., & Schlissel, M. S. (2002) · Nature Immunology · doi:10.1038/ni870 · Cited by 164
DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes
Bredemeyer, A. L., Helmink, B. A., Innes, C. L., Calderón, B., McGinnis, L. M., Mahowald, G. K., Gapud, E. J., Walker, L. M., Collins, J. B., Weaver, B. K., et al. (2008) · Nature · doi:10.1038/nature07392 · Cited by 154
Self-citationH2AX chromatin structures and their response to DNA damage revealed by 4Pi microscopy
Bewersdorf, J., Bennett, B. T., & Knight, K. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608709103 · Cited by 125
Kimurâ, H., Takizawa, N., Allemand, E., Hori, T., Iborra, F. J., Nozaki, N., Muraki, M., Hagiwara, M., Krainer, A. R., Fukagawa, T., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200608001 · Cited by 86
Bassing, C. H., Ranganath, S. H., Murphy, M., Savic, V., Gleason, M., & Alt, F. W. (2007) · Blood · doi:10.1182/blood-2007-08-104760 · Cited by 18
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Mah, L.-J., El-Osta, A., & Karagiannis, T. C. (2010) · Leukemia · doi:10.1038/leu.2010.6 · Cited by 1,557
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Marechal, A., & Zou, L. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012716 · Cited by 1,514
Lukas, C., Savic, V., Bekker‐Jensen, S., Doil, C., Neumann, B., Pedersen, R. S., Grøfte, M., Chan, K., Hickson, I. D., Bártek, J., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2201 · Cited by 701
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Metadata
- Authors
- Savic, V., Yin, B., Maas, N. L., Bredemeyer, A. L., Carpenter, A. C., Helmink, B. A., Yang-Iott, K. S., Sleckman, B. P., & Bassing, C. H.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Washington University in St. Louis (US)
- Corresponding author
- Bassing, Craig H.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 34
- Issue
- 3
- Pages
- 298-310
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2744111
- OpenAlex
- W2036749550
- Cited by
- 204
- References
- 48
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 14 · 2023: 9 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 12 · 2018: 7 · 2017: 12 · 2016: 9 · 2015: 9 · 2014: 12 · 2013: 22 · 2012: 15
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1574 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion)
- Funders
- National Cancer Institute (R01CA125195)
- National Institute of Allergy and Infectious Diseases (R01AI074953, T32AI055428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- γH2AX, DNA double-strand breaks, ATM, MDC1, DNA-PKcs, H2AX phosphorylation, DNA repair, G1 phase, chromatin
- MeSH terms
- Animals, B-Lymphocytes, Chromatin, DNA, DNA Damage, DNA-Binding Proteins, Endonucleases, Histones, Nuclear Proteins, Recombination, Genetic, Thymus Gland, Tumor Suppressor Protein p53, G1 Phase, Protein Serine-Threonine Kinases, Mice, Knockout, Cell Cycle Proteins, Genes, T-Cell Receptor alpha, Tumor Suppressor Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, Ataxia Telangiectasia Mutated Proteins
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