Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage
Open accessAbstract
BRCA1 (BReast‐CAncer susceptibility gene 1) and BRCA2 are tumor suppressor genes, the mutant phenotypes of which predispose to breast and ovarian cancers. Intensive research has shown that BRCA proteins are involved in a multitude of pivotal cellular processes. In particular, both genes contribute to DNA repair and transcriptional regulation in response to DNA damage. Recent studies suggest that BRCA proteins are required for maintenance of chromosomal stability, thereby protecting the genome from damage. New data also show that BRCAs transcriptionally regulate some genes involved in DNA repair, the cell cycle, and apo ptosis. Many of these functions are mediated by a large number of cellular proteins that interact with BRCAs. The functions of BRCA proteins are also linked to distinct and specific phosphory‐lation events; however, the extent to which phosphorylation‐acti‐vated molecular pathways contribute to tumor suppressor activity remains unclear. Finally, the reasons why mutations in BRCA genes lead to the development of breast and ovarian cancers are not clearly understood. Elucidation of the precise molecular functions of BRCAs is expected to improve our understanding of hereditary as well as sporadic mammary carcinogenesis.
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Brca1 is a component of homologous recombination repair machinery, and BRCA1 is uncommonly mutated in PDAC (~1%), typically germline, and associated with HRR defective cancers.
“The encoded Brca1 protein is a component of the homologous recombination repair (HRR) machinery, and BRCA1 is uncommonly mutated in PDAC (~1%), typically in the germline, and associated with HRR defective cancers22,23.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [22]
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- Authors
- Yoshida, K., & Miki, Y.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Miki, Yoshio
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2004-11
- Volume
- 95
- Issue
- 11
- Pages
- 866-871
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC11159131
- OpenAlex
- W2118498634
- Cited by
- 753
- References
- 62
- Citations by year
- 2026: 33 · 2025: 39 · 2024: 66 · 2023: 87 · 2022: 54 · 2021: 45 · 2020: 50 · 2019: 31 · 2018: 38 · 2017: 37 · 2016: 35 · 2015: 26 · 2014: 32 · 2013: 19 · 2012: 15
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- BRCA1, BRCA2, DNA repair, DNA damage response, transcriptional regulation, cell cycle regulation, chromosome stability, tumor suppressor, breast cancer, ovarian cancer, protein phosphorylation, protein-protein interaction, apoptosis, mammary carcinogenesis
- MeSH terms
- Breast Neoplasms, Cell Cycle, DNA Damage, DNA Repair, Female, Humans, Mutation, Ovarian Neoplasms, Phosphorylation, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Apoptosis, Genes, BRCA1, Genes, BRCA2
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