Skip to main content
SpringerLink
Log in

Interplay Between γH2AX and 53BP1 Pathways in DNA Double-Strand Break Repair Response

  • Chapter
Apoptosis, Senescence, and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

summary

One of the most fascinating themes in the biology of double-strand breaks (DSBs) is that chromatin is emerging as a multifunctional player in the DSB damage response. The phosphorylation of H2AX on Ser 139, named γH2AX, is an early response to the generation of DNA DSBs and extends along megabase-long domains, both sites of the lesion, supporting amplification of signal transduction pathways. In parallel, 53BP1 accumulates on damaged chromatin to interface between methylated histone residues and proteins that belong to the signal-transduction pathways, mediating cell-cycle arrest or apoptosis. Interestingly, the two pathways crosstalk at the chromatin level.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. van den Bosch M, Lohman PH, Pastink A. DNA double-strand break repair by homologous recombination. Biol Chem 2002;383(6):873–92.

    Article  PubMed  Google Scholar 

  2. Rothkamm K, Kruger I, Thompson LH, Lobrich M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 2003;23(16):5706–15.

    Article  PubMed  CAS  Google Scholar 

  3. Weterings E, van Gent DC. The mechanism of non-homologous end-joining: a synopsis of synapsis. DNA Repair (Amst) 2004;3(11):1425–35.

    Article  CAS  Google Scholar 

  4. Lees-Miller SP, Meek K. Repair of DNA double strand breaks by non-homologous end joining. Biochimie 2003;85(11):1161–73.

    Article  PubMed  CAS  Google Scholar 

  5. Kaina B. DNA damage-triggered apoptosis: critical role of DNA repair, double-strand breaks, cell proliferation and signaling. Biochem Pharmacol 2003;66(8):1547–54.

    Article  PubMed  CAS  Google Scholar 

  6. Jackson SP. Sensing and repairing DNA double-strand breaks. Carcinogenesis 2002;23(5):687–96.

    Article  PubMed  CAS  Google Scholar 

  7. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 1999;146(5):905–16.

    Article  PubMed  CAS  Google Scholar 

  8. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 1998;273(10):5858–68.

    Article  PubMed  CAS  Google Scholar 

  9. Redon C, Pilch D, Rogakou E, Sedelnikova O, Newrock K, Bonner W. Histone H2A variants H2AX and H2AZ. Curr Opin Genet Dev 2002;12(2):162–9.

    Article  PubMed  CAS  Google Scholar 

  10. Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH, Haber JE, Lichten M. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 2004;14(19):1703–11.

    Article  PubMed  CAS  Google Scholar 

  11. Unal E, Arbel-Eden A, Sattler U, et al. DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 2004;16(6):991–1002.

    Article  PubMed  Google Scholar 

  12. Bassing CH, Alt FW. The cellular response to general and programmed DNA double strand breaks. DNA Repair (Amst) 2004;3(8–9):781–96.

    Article  CAS  Google Scholar 

  13. Bassing CH, Suh H, Ferguson DO, et al. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 2003;114(3):359–70.

    Article  PubMed  CAS  Google Scholar 

  14. Chen HT, Bhandoola A, Difilippantonio MJ, et al. Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX. Science 2000;290(5498):1962–5.

    Article  PubMed  CAS  Google Scholar 

  15. Nakamura TM, Du LL, Redon C, Russell P. Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Mol Cell Biol 2004;24(14):6215–30.

    Article  PubMed  CAS  Google Scholar 

  16. Downs JA, Lowndes NF, Jackson SP. A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature 2000;408(6815):1001–4.

    Article  PubMed  CAS  Google Scholar 

  17. Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001;276(45):42462–7.

    Article  PubMed  CAS  Google Scholar 

  18. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 2003;3(3):155–68.

    Article  PubMed  CAS  Google Scholar 

  19. Riballo E, Kuhne M, Rief N, et al. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Mol Cell 2004;16(5):715–24.

    Article  PubMed  CAS  Google Scholar 

  20. Stiff T, O’Driscoll M, Rief N, Iwabuchi K, Lobrich M, Jeggo PA. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res 2004;64(7):2390–6.

    Article  PubMed  CAS  Google Scholar 

  21. Andegeko Y, Moyal L, Mittelman L, Tsarfaty I, Shiloh Y, Rotman G. Nuclear retention of ATM at sites of DNA double strand breaks. J Biol Chem 2001;276(41):38224–30.

    PubMed  CAS  Google Scholar 

  22. Hammond EM, Dorie MJ, Giaccia AJ. ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. J Biol Chem 2003;278(14):12207–13.

    Article  PubMed  CAS  Google Scholar 

  23. Ward IM, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 2001;276(51):47759–62.

    PubMed  CAS  Google Scholar 

  24. Furuta T, Takemura H, Liao ZY, 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(22):20303–12.

    Article  PubMed  CAS  Google Scholar 

  25. Koundrioukoff S, Polo S, Almouzni G. Interplay between chromatin and cell cycle checkpoints in the context of ATR/ATM-dependent checkpoints. DNA Repair (Amst) 2004;3(8–9):969–78.

    Article  CAS  Google Scholar 

  26. Fernandez-Capetillo O, Lee A, Nussenzweig M, Nussenzweig A. H2AX: the histone guardian of the genome. DNA Repair (Amst) 2004;3(8–9):959–67.

    Article  CAS  Google Scholar 

  27. Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 2000;10(15):886–95.

    Article  PubMed  CAS  Google Scholar 

  28. Chan DW, Chen BP, Prithivirajsingh S, et al. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev 2002;16(18):2333–8.

    Article  PubMed  CAS  Google Scholar 

  29. Siino JS, Nazarov IB, Svetlova MP, et al. Photobleaching of GFP-labeled H2AX in chromatin: H2AX has low diffusional mobility in the nucleus. Biochem Biophys Res Commun 2002;297(5):1318–23.

    Article  PubMed  CAS  Google Scholar 

  30. Sedelnikova OA, Pilch DR, Redon C, Bonner WM. Histone H2AX in DNA damage and repair. Cancer Biol Ther 2003;2(3):233–5.

    PubMed  CAS  Google Scholar 

  31. Pilch DR, Sedelnikova OA, Redon C, Celeste A, Nussenzweig A, Bonner WM. Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 2003;81(3):123–9.

    Article  PubMed  CAS  Google Scholar 

  32. Fernandez-Capetillo O, Celeste A, Nussenzweig A. Focusing on foci: H2AX and the recruitment of DNA-damage response factors. Cell Cycle 2003;2(5):426–7.

    PubMed  CAS  Google Scholar 

  33. Celeste A, Fernandez-Capetillo O, Kruhlak MJ, et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 2003;5(7):675–9.

    Article  PubMed  CAS  Google Scholar 

  34. Celeste A, Difilippantonio S, Difilippantonio MJ, et al. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 2003;114(3):371–83.

    Article  PubMed  CAS  Google Scholar 

  35. Goldberg M, Stucki M, Falck J, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 2003;421(6926):952–6.

    Article  PubMed  CAS  Google Scholar 

  36. Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 2003;421(6926):961–6.

    Article  PubMed  CAS  Google Scholar 

  37. Stucki M, Jackson SP. MDC1/NFBD1: a key regulator of the DNA damage response in higher eukaryotes. DNA Repair (Amst) 2004;3(8–9):953–7.

    Article  CAS  Google Scholar 

  38. Xu X, Stern DF. NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors. FASEB J 2003;17(13):1842–8.

    Article  PubMed  CAS  Google Scholar 

  39. Peng A, Chen PL. NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage. J Biol Chem 2003;278(11):8873–6.

    Article  PubMed  CAS  Google Scholar 

  40. Lukas C, Melander F, Stucki M, et al. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J 2004;23(13):2674–83.

    Article  PubMed  CAS  Google Scholar 

  41. Mochan TA, Venere M, DiTullio RA Jr, Halazonetis TD. 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage. Cancer Res 2003;63(24):8586–91.

    PubMed  CAS  Google Scholar 

  42. Shang YL, Bodero AJ, Chen PL. NFBD1, a novel nuclear protein with signature motifs of FHA and BRCT, and an internal 41-amino acid repeat sequence, is an early participant in DNA damage response. J Biol Chem 2003;278(8):6323–9.

    Article  PubMed  CAS  Google Scholar 

  43. Manke IA, Lowery DM, Nguyen A, Yaffe MB. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 2003;302(5645):636–9.

    Article  PubMed  CAS  Google Scholar 

  44. Lee MS, Edwards RA, Thede GL, Glover JN. Structure of the BRCT repeat domain of MDC1 and its specificity for the free COOH-terminal end of the ⌊gamma⌋-H2AX histone tail. J Biol Chem 2005;280(37):32053–6.

    Article  PubMed  CAS  Google Scholar 

  45. Peng A, Chen PL. NFBD1/Mdc1 mediates ATR-dependent DNA damage response. Cancer Res 2005;65(4):1158–63.

    Article  PubMed  CAS  Google Scholar 

  46. Lee AC, Fernandez-Capetillo O, Pisupati V, Jackson SP, Nussenzweig A. Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage. Cell Cycle 2005;4(1):177–82.

    PubMed  CAS  Google Scholar 

  47. Bekker-Jensen S, Lukas C, Melander F, Bartek J, Lukas J. Dynamic assembly and sustained retention of 53BP1 at the sites of DNA damage are controlled by Mdc1/NFBD1. J Cell Biol 2005;170(2):201–11.

    Article  PubMed  CAS  Google Scholar 

  48. D’Amours D, Jackson SP. The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat Rev Mol Cell Biol 2002;3(5):317–27.

    Article  PubMed  CAS  Google Scholar 

  49. Petrini JH, Stracker TH. The cellular response to DNA double-strand breaks: defining the sensors and mediators. Trends Cell Biol 2003;13(9):458–62.

    Article  PubMed  CAS  Google Scholar 

  50. Costanzo V, Robertson K, Bibikova M, et al. Mre11 protein complex prevents double-strand break accumulation during chromosomal DNA replication. Mol Cell 2001;8(1):137–47.

    Article  PubMed  CAS  Google Scholar 

  51. Moreno-Herrero F, de Jager M, Dekker NH, Kanaar R, Wyman C, Dekker C. Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature 2005;437(7057):440–3.

    Article  PubMed  CAS  Google Scholar 

  52. Williams RS, Tainer JA. A nanomachine for making ends meet: MRN is a flexing scaffold for the repair of DNA double-strand breaks. Mol Cell 2005;19(6):724–6.

    Article  PubMed  CAS  Google Scholar 

  53. Kobayashi J, Antoccia A, Tauchi H, Matsuura S, Komatsu K. NBS1 and its functional role in the DNA damage response. DNA Repair (Amst) 2004;3(8–9):855–61.

    Article  CAS  Google Scholar 

  54. Kobayashi J, Tauchi H, Sakamoto S, et al. NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain. Curr Biol 2002;12(21):1846–51.

    Article  PubMed  CAS  Google Scholar 

  55. Kang J, Ferguson D, Song H, et al. Functional Interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression. Mol Cell Biol 2005;25(2):661–70.

    Article  PubMed  CAS  Google Scholar 

  56. Horejsi Z, Falck J, Bakkenist CJ, Kastan MB, Lukas J, Bartek J. Distinct functional domains of Nbs1 modulate the timing and magnitude of ATM activation after low doses of ionizing radiation. Oncogene 2004;23(17):3122–7.

    Google Scholar 

  57. Difilippantonio S, Celeste A, Fernandez-Capetillo O, et al. Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models. Nat Cell Biol 2005;7(7):675–85.

    Article  PubMed  CAS  Google Scholar 

  58. Lee JH, Paull TT. Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 2004;304(5667):93–6.

    Article  PubMed  CAS  Google Scholar 

  59. Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 2003;22(20):5612–21.

    Article  PubMed  CAS  Google Scholar 

  60. Girard PM, Riballo E, Begg AC, Waugh A, Jeggo PA. Nbs1 promotes ATM dependent phosphorylation events including those required for G1/S arrest. Oncogene 2002;21(27):4191–9.

    Article  PubMed  CAS  Google Scholar 

  61. You Z, Chahwan C, Bailis J, Hunter T, Russell P. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol 2005;25(13):5363–79.

    Article  PubMed  CAS  Google Scholar 

  62. Lee AC, Fernandez-Capetillo O, Pisupati V, Jackson SP, Nussenzweig A. Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage. Cell Cycle 2005;4(1):177–82.

    PubMed  CAS  Google Scholar 

  63. Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S. Two cellular proteins that bind to wild-type but not mutant p53. Proc Natl Acad Sci USA 1994;91(13):6098–102.

    Article  PubMed  CAS  Google Scholar 

  64. Schultz LB, Chehab NH, Malikzay A, Halazonetis TD. p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J Cell Biol 2000;151(7):1381–90.

    Article  PubMed  CAS  Google Scholar 

  65. Anderson L, Henderson C, Adachi Y. Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage. Mol Cell Biol 2001;21(5):1719–29.

    Article  PubMed  CAS  Google Scholar 

  66. Rappold I, Iwabuchi K, Date T, Chen J. Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways. J Cell Biol 2001;153(3):613–20.

    Article  PubMed  CAS  Google Scholar 

  67. Sengupta S, Robles AI, Linke SP, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol 2004;166(6):801–13.

    Article  PubMed  CAS  Google Scholar 

  68. Richie CT, Peterson C, Lu T, Hittelman WN, Carpenter PB, Legerski RJ. hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage. Mol Cell Biol 2002;22(24):8635–47.

    Article  PubMed  CAS  Google Scholar 

  69. Ward IM, Minn K, Jorda KG, Chen J. Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. J Biol Chem 2003;278(22):19579–82.

    Article  PubMed  CAS  Google Scholar 

  70. Kao GD, McKenna WG, Guenther MG, Muschel RJ, Lazar MA, Yen TJ. Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. J Cell Biol 2003;160(7):1017–27.

    Article  PubMed  CAS  Google Scholar 

  71. Mochan TA, Venere M, DiTullio RA Jr, Halazonetis TD. 53BP1, an activator of ATM in response to DNA damage. DNA Repair (Amst) 2004;3(8–9):945–52.

    Article  CAS  Google Scholar 

  72. Huyen Y, Zgheib O, Ditullio RA Jr, et al. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 2004;432(7015):406–11.

    Article  PubMed  CAS  Google Scholar 

  73. Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP. Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Genes Dev 2002;16(5):583–93.

    Article  PubMed  CAS  Google Scholar 

  74. Derbyshire DJ, Basu BP, Serpell LC, et al. Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor. EMBO J 2002;21(14):3863–72.

    Article  PubMed  CAS  Google Scholar 

  75. Lo KW, Kan HM, Chan LN, et al. The 8 kDa dynein light chain binds to 53BP1 and mediates DNA damage-induced p53 nuclear accumulation. J Biol Chem 2005;280(9):8172–9.

    Article  PubMed  CAS  Google Scholar 

  76. Charier G, Couprie J, Alpha-Bazin B, et al. The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding. Structure (Camb) 2004;12(9):1551–62.

    Article  CAS  Google Scholar 

  77. Iwabuchi K, Basu BP, Kysela B, et al. Potential role for 53BP1 in DNA end-joining repair through direct interaction with DNA. J Biol Chem 2003;278(38):36487–95.

    Article  PubMed  CAS  Google Scholar 

  78. Fernandez-Capetillo O, Chen HT, Celeste A, et al. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol 2002;4(12):993–7.

    Article  PubMed  CAS  Google Scholar 

  79. Jullien D, Vagnarelli P, Earnshaw WC, Adachi Y. Kinetochore localisation of the DNA damage response component 53BP1 during mitosis. J Cell Sci 2002;115(Pt 1):71–9.

    PubMed  CAS  Google Scholar 

  80. Abraham RT. Checkpoint signalling: focusing on 53BP1. Nat Cell Biol 2002;4(12):E277–9.

    Article  PubMed  CAS  Google Scholar 

  81. Wang B, Matsuoka S, Carpenter PB, Elledge SJ. 53BP1, a mediator of the DNA damage checkpoint. Science 2002;298(5597):1435–8.

    Article  PubMed  CAS  Google Scholar 

  82. DiTullio RA Jr, Mochan TA, Venere M, et al. 53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer. Nat Cell Biol 2002;4(12):998–1002.

    Article  PubMed  CAS  Google Scholar 

  83. Wysocki R, Javaheri A, Allard S, Sha F, Cote J, Kron SJ. Role of dot1-dependent histone h3 methylation in g1 and s phase DNA damage checkpoint functions of rad9. Mol Cell Biol 2005;25(19):8430–43.

    Article  PubMed  CAS  Google Scholar 

  84. Sanders SL, Portoso M, Mata J, Bahler J, Allshire RC, Kouzarides T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 2004;119(5):603–14.

    Article  PubMed  CAS  Google Scholar 

  85. Onclercq-Delic R, Calsou P, Delteil C, Salles B, Papadopoulo D, Amor-Gueret M. Possible anti-recombinogenic role of Bloom’s syndrome helicase in double-strand break processing. Nucleic Acids Res 2003;31(21):6272–82.

    Article  PubMed  CAS  Google Scholar 

  86. Celeste A, Petersen S, Romanienko PJ, et al. Genomic instability in mice lacking histone H2AX. Science 2002;296(5569):922–7.

    Article  PubMed  CAS  Google Scholar 

  87. Zgheib O, Huyen Y, Ditullio RA Jr, et al. ATM signaling and 53BP1. Radiother Oncol 2005;76(2):119–22.

    Article  PubMed  CAS  Google Scholar 

  88. Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003;421(6922):499–506n.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Fatouros Chronis BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emmy P. Rogakou PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA

    David A. Gewirtz

  2. Departments of Medicine, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Shawn E. Holt

  3. Departments of Pathology, Human Genetics, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Steven Grant

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc.

About this chapter

Cite this chapter

Chronis, F., Rogakou, E.P. (2007). Interplay Between γH2AX and 53BP1 Pathways in DNA Double-Strand Break Repair Response. In: Gewirtz, D.A., Holt, S.E., Grant, S. (eds) Apoptosis, Senescence, and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-221-2_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-221-2_13

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-527-9

  • Online ISBN: 978-1-59745-221-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation