The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
BRCA1 tumour suppression occurs via heterochromatin-mediated silencing
Open accessAbstract
Mutations in tumor suppressor BRCA1 lead to breast and/or ovarian cancer. Here we show that loss of BRCA1 in mice results in transcriptional derepression of the tandemly repeated satellite DNA. BRCA1 deficiency is accompanied by reduction of condensed DNA regions in the genome and loss of ubiquitylation of histone H2A at satellite repeats. BRCA1 binds to satellite DNA regions in vivo and ubiquitylates H2A in vitro. Ectopic expression of an H2A fused to ubiquitin reverses the effects of BRCA1 loss, suggesting that BRCA1 maintains heterochromatin structure via ubiquitylation of histone H2A. Satellite DNA derepression was also observed mouse and human BRCA1 deficient breast cancers. Ectopic expression of satellite DNA can phenocopy BRCA1 loss in centrosome amplification, cell cycle checkpoint defects, DNA damage and genomic instability. We propose that the role of BRCA1 in maintaining global heterochromatin integrity accounts for many of its tumor suppressor functions.
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Cites
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Cited by
Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins
Prakash, R., Zhang, Y., Feng, W., & Jasin, M. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016600 · Cited by 869
Regulation of DNA Damage Responses by Ubiquitin and SUMO
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Constitutive heterochromatin formation and transcription in mammals
Saksouk, N., Simboeck, E., & Déjardin, J. (2015) · Epigenetics & Chromatin · doi:10.1186/1756-8935-8-3 · Cited by 543
Microsatellite instability: a review of what the oncologist should know
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Metadata
- Authors
- Zhu, Q., Pao, G. M., Huynh, A. M., Suh, H., Tonnu, N., Nederlof, P. M., Gage, F. H., & Verma, I. M.
- Venue
- Nature
- Published
- 2011-09
- Volume
- 477
- Issue
- 7363
- Pages
- 179-184
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2093385884
- Cited by
- 485
- References
- 29
- FWCI
- 17.28
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhu, Q., Pao, G. M., Huynh, A. M., Suh, H., Tonnu, N., Nederlof, P. M., Gage, F. H., & Verma, I. M. (2011). BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature. https://doi.org/10.1038/nature10371
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