ArticleNucleic acids research2014
A portable BRCA1-HAC (human artificial chromosome) module for analysis of BRCA1 tumor suppressor function.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
- Synthetic rewriting technologies in mammalian cells.Nature communications · 2026Review
- Article
- Therapy enhancing chromosome instability may be advantageous forNAR cancer · 2025Article
- The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability.Cell reports · 2025Article
- Review
- Assembly of Multiple Full-Size Genes or Genomic DNA Fragments on Human Artificial Chromosomes Using the Iterative Integration System.Current protocols · 2021Article
- Highly Efficient Microcell-Mediated Transfer of HACs Containing a Genomic Region of Interest into Mammalian Cells.Current protocols · 2021Article
- Highly Selective, CRISPR/Cas9-Mediated Isolation of Genes and Genomic Loci from Complex Genomes by TAR Cloning in Yeast.Current protocols · 2021Article
- Analysis of Complex DNA Rearrangements during Early Stages of HAC Formation.ACS synthetic biology · 2020Article
- A novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission.Genome research · 2019Article
- TAR Cloning: Perspectives for Functional Genomics, Biomedicine, and Biotechnology.Molecular therapy. Methods & clinical development · 2019Review
- BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression.Cancers · 2018Review
- Human Artificial Chromosome with Regulated Centromere: A Tool for Genome and Cancer Studies.ACS synthetic biology · 2018Review
- Method to Assemble Genomic DNA Fragments or Genes on Human Artificial Chromosome with Regulated Kinetochore Using a Multi-Integrase System.ACS synthetic biology · 2018Article
- The Mitotic and Metabolic Effects of Phosphatidic Acid in the Primary Muscle Cells of Turbot (Frontiers in endocrinology · 2018Article
- Review
- Core Concept: Human artificial chromosomes offer insights, therapeutic possibilities, and challenges.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Epigenetic engineering reveals a balance between histone modifications and transcription in kinetochore maintenance.Nature communications · 2016Article
- Transformation-associated recombination (TAR) cloning for genomics studies and synthetic biology.Chromosoma · 2016Review
- Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
BRCA1 is involved in many disparate cellular functions, including DNA damage repair, cell-cycle checkpoint activation, gene transcriptional regulation, DNA replication, centrosome function and others. The majority of evidence strongly favors the maintenance of genomic integrity as a principal tumor suppressor activity of BRCA1. At the same time some functional aspects of BRCA1 are not fully understood. Here, a HAC (human artificial chromosome) module with a regulated centromere was constructed for delivery and expression of the 90 kb genomic copy of the BRCA1 gene into BRCA1-deficient human cells. A battery of functional tests was carried out to demonstrate functionality of the exogenous BRCA1. In separate experiments, we investigated the role of BRCA1 in maintenance of heterochromatin integrity within a human functional kinetochore. We demonstrated that BRCA1 deficiency results in a specific activation of transcription of higher-order alpha-satellite repeats (HORs) assembled into heterochromatin domains flanking the kinetochore. At the same time no detectable elevation of transcription was observed within HORs assembled into centrochromatin domains. Thus, we demonstrated a link between BRCA1 deficiency and kinetochore dysfunction and extended previous observations that BRCA1 is required to silence transcription in heterochromatin in specific genomic loci. This supports the hypothesis that epigenetic alterations of the kinetochore initiated in the absence of BRCA1 may contribute to cellular transformation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.