The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation
Open accessAbstract
H2AX phosphorylation is an early step in the response to DNA damage. It is widely accepted that ATM (ataxia telangiectasia mutated protein) phosphorylates H2AX in response to DNA double-strand breaks (DSBs). Whether DNA-dependent protein kinase (DNA-PK) plays any role in this response is unclear. Here, we show that H2AX phosphorylation after exposure to ionizing radiation (IR) occurs to similar extents in human fibroblasts and in mouse embryo fibroblasts lacking either DNA-PK or ATM but is ablated in ATM-deficient cells treated with LY294002, a drug that specifically inhibits DNA-PK. Additionally, we show that inactivation of both DNA-PK and ATM is required to ablate IR-induced H2AX phosphorylation in chicken cells. We confirm that H2AX phosphorylation induced by DSBs in nonreplicating cells is ATR (ataxia telangiectasia and Rad3-related protein) independent. Taken together, we conclude that under most normal growth conditions, IR-induced H2AX phosphorylation can be carried out by ATM and DNA-PK in a redundant, overlapping manner. In contrast, DNA-PK cannot phosphorylate other proteins involved in the checkpoint response, including chromatin-associated Rad17. However, by phosphorylating H2AX, DNA-PK can contribute to the presence of the damage response proteins MDC1 and 53BP1 at the site of the DSB.
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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
The DNA damage response: putting checkpoints in perspective
Zhou, B.-B. S., & Elledge, S. J. (2000) · Nature · doi:10.1038/35044005 · Cited by 3,213
A Single Ataxia Telangiectasia Gene with a Product Similar to PI-3 Kinase
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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
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Rothkamm, K., & Löbrich, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0830918100 · Cited by 1,645
Self-citationGenomic 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
Histone 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
O'Driscoll, M., Ruiz-Perez, V. L., Woods, C. G., Jeggo, P. A., & Goodship, J. A. (2003) · Nature Genetics · doi:10.1038/ng1129 · Cited by 794
Self-citationMDC1 is required for the intra-S-phase DNA damage checkpoint
Goldberg, M., Stucki, M., Falck, J., D'Amours, D., Rahman, D., Pappin, D., Bartek, J., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature01445 · Cited by 506
Cited by
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
Lieber, M. R. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.052308.093131 · Cited by 2,882
Bonner, W. M., Redon, C. E., Dickey, J. S., Nakamura, A. J., Sedelnikova, O. A., Solier, S., & Pommier, Y. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2523 · Cited by 1,623
γH2AX: a sensitive molecular marker of DNA damage and repair
Mah, L.-J., El-Osta, A., & Karagiannis, T. C. (2010) · Leukemia · doi:10.1038/leu.2010.6 · Cited by 1,557
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
Falck, J., Coates, J., & Jackson, S. P. (2005) · Nature · doi:10.1038/nature03442 · Cited by 1,258
-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin
Kinner, A., Wu, W., Staudt, C., & Iliakis, G. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn550 · Cited by 1,256
Metadata
- Authors
- Stiff, T., O’Driscoll, M., Rief, N., Iwabuchi, K., Löbrich, M., & Jeggo, P. A.
- Venue
- Cancer Research
- Published
- 2004-04-01
- Volume
- 64
- Issue
- 7
- Pages
- 2390-2396
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2143629217
- Cited by
- 1,014
- References
- 12
- FWCI
- 20.01
- Type
- journal article
- Language
- en
- Open access
- green
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- Stiff, T., O’Driscoll, M., Rief, N., Iwabuchi, K., Löbrich, M., & Jeggo, P. A. (2004). ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation. Cancer Research. https://doi.org/10.1158/0008-5472.can-03-3207
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