The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Nuclear phosphoinositide 3-kinase β controls double-strand break DNA repair
Open accessAbstract
Class I phosphoinositide 3-kinases are enzymes that generate 3-poly-phosphoinositides at the cell membrane following transmembrane receptor stimulation. Expression of the phosphoinositide 3-kinase β (PI3Kβ) isoform, but not its activity, is essential for early embryonic development. Nonetheless, the specific function of PI3Kβ in the cell remains elusive. Double-strand breaks (DSB) are among the most deleterious lesions for genomic integrity; their repair is required for development. We show that PI3Kβ is necessary for DSB sensing, as PI3Kβ regulates binding of the Nbs1 sensor protein to damaged DNA. Indeed, Nbs1 did not bind to DSB in PI3Kβ-deficient cells, which showed a general defect in subsequent ATM and ATR activation, resulting in genomic instability. Inhibition of PI3Kβ also retarded the DNA repair but the defect was less marked than that induced by PI3Kβ deletion, supporting a kinase-independent function for PI3Kβ in DNA repair. These results point at class I PI3Kβ as a critical sensor of genomic integrity.
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Cites
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317
Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage.
Lukas, C., Falck, J., Bartkova, J., Bartek, J., & Lukas, J. (2003) · Nature Cell Biology · doi:10.1038/ncb945 · Cited by 474
Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation
Foukas, L. C., Claret, M., Pearce, W., Okkenhaug, K., Meek, S., Peskett, E., Sancho, S., Smith, A. J. H., Withers, D. J., & Vanhaesebroeck, B. (2006) · Nature · doi:10.1038/nature04694 · Cited by 463
Cited by
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
Ibrahim, Y. H., García-García, C., Serra, V., He, L., Torres-Lockhart, K., Prat, A., Anton, P., Cozar, P., Guzmán, M., Grueso, J., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0348 · Cited by 601
Juvekar, A., Burga, L. N., Hu, H., Lunsford, E. P., Ibrahim, Y. H., Balmañà, J., Rajendran, A., Papa, A., Spencer, K., Lyssiotis, C. A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0336 · Cited by 465
Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review
Costa, R. L. B., Han, H. S., & Gradishar, W. J. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4697-y · Cited by 439
New Strategies for Triple-Negative Breast Cancer—Deciphering the Heterogeneity
Mayer, I. A., Abramson, V. G., Lehmann, B. D., & Pietenpol, J. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0583 · Cited by 320
Metadata
- Authors
- Kumar, A., Fernandez-Capetillo, O., & Carrera, A. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-04-05
- Volume
- 107
- Issue
- 16
- Pages
- 7491-7496
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2117988802
- Cited by
- 165
- References
- 3
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- green
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