The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
BRCA1-BARD1 Complexes Are Required for p53Ser-15 Phosphorylation and a G1/S Arrest following Ionizing Radiation-induced DNA Damage
Open accessAbstract
BRCA1 is a major player in the DNA damage response. This is evident from its loss, which causes cells to become sensitive to a wide variety of DNA damaging agents. The major BRCA1 binding partner, BARD1, is also implicated in the DNA damage response, and recent reports indicate that BRCA1 and BARD1 co-operate in this pathway. In this report, we utilized small interfering RNA to deplete BRCA1 and BARD1 to demonstrate that the BRCA1-BARD1 complex is required for ATM/ATR (ataxia-telangiectasia-mutated/ATM and Rad3-related)-mediated phosphorylation of p53(Ser-15) following IR- and UV radiation-induced DNA damage. In contrast, phosphorylation of a number of other ATM/ATR targets including H2AX, Chk2, Chk1, and c-jun does not depend on the presence of BRCA1-BARD1 complexes. Moreover, prior ATM/ATR-dependent phosphorylation of BRCA1 at Ser-1423 or Ser-1524 regulates the ability of ATM/ATR to phosphorylate p53(Ser-15) efficiently. Phosphorylation of p53(Ser-15) is necessary for an IR-induced G(1)/S arrest via transcriptional induction of the cyclin-dependent kinase inhibitor p21. Consistent with these data, repressing p53(Ser-15) phosphorylation by BRCA1-BARD1 depletion compromises p21 induction and the G(1)/S checkpoint arrest in response to IR but not UV radia-tion. These findings suggest that BRCA1-BARD1 complexes act as an adaptor to mediate ATM/ATR-directed phosphorylation of p53, influencing G(1)/S cell cycle progression after DNA damage.
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Cites
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ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
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Genomic Instability in Mice Lacking Histone H2AX
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Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks
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MDC1 is a mediator of the mammalian DNA damage checkpoint
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MDC1 is required for the intra-S-phase DNA damage checkpoint
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Cited by
DNA Damage Sensing by the ATM and ATR Kinases
Marechal, A., & Zou, L. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012716 · Cited by 1,514
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer
Huang, R.-X., & Zhou, P.-K. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0150-x · Cited by 1,198
The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability
Gudmundsdottir, K., & Ashworth, A. (2006) · Oncogene · doi:10.1038/sj.onc.1209874 · Cited by 622
Transcriptional Regulation by P53
Beckerman, R., & Prives, C. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000935 · Cited by 569
BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution
Deng, C.-X. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl010 · Cited by 584
Metadata
- Authors
- Fabbro, M., Savage, K., Hobson, K., Deans, A. J., Powell, S. N., McArthur, G. A., & Khanna, K. K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 30
- Pages
- 31251-31258
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2026007913
- Cited by
- 163
- References
- 16
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Fabbro, M., Savage, K., Hobson, K., Deans, A. J., Powell, S. N., McArthur, G. A., & Khanna, K. K. (2004). BRCA1-BARD1 Complexes Are Required for p53Ser-15 Phosphorylation and a G1/S Arrest following Ionizing Radiation-induced DNA Damage. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m405372200
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