ArticlePloS one2013
Requirement of heterogeneous nuclear ribonucleoprotein C for BRCA gene expression and homologous recombination.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 61 citations in OpenAlex.
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- Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks.Scientific reports · 2024Article
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- Advances in the study of RNA-binding proteins in diabetic complications.Molecular metabolism · 2022Review
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- HNRNPC regulates RhoA to induce DNA damage repair and cancer-associated fibroblast activation causing radiation resistance in pancreatic cancer.Journal of cellular and molecular medicine · 2022Article
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- ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses.The Journal of experimental medicine · 2021Article
- The mRNA (New York, N.Y.) · 2021Article
- PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.Nature communications · 2021Article
- The human nucleoporin Tpr protects cells from RNA-mediated replication stress.Nature communications · 2021Article
- Identification of genetic variants in mArchives of toxicology · 2021Article
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- New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response.Frontiers in molecular biosciences · 2021Review
- Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHeterogeneous nuclear ribonucleoprotein C1/C2 (hnRNP C) is a core component of 40S ribonucleoprotein particles that bind pre-mRNAs and influence their processing, stability and export. Breast cancer tumor suppressors BRCA1, BRCA2 and PALB2 form a complex and play key roles in homologous recombination (HR), DNA double strand break (DSB) repair and cell cycle regulation following DNA damage.
methodsPALB2 nucleoprotein complexes were isolated using tandem affinity purification from nuclease-solubilized nuclear fraction. Immunofluorescence was used for localization studies of proteins. siRNA-mediated gene silencing and flow cytometry were used for studying DNA repair efficiency and cell cycle distribution/checkpoints. The effect of hnRNP C on mRNA abundance was assayed using quantitative reverse transcriptase PCR. RESULTS AND SIGNIFICANCE: We identified hnRNP C as a component of a nucleoprotein complex containing breast cancer suppressor proteins PALB2, BRCA2 and BRCA1. Notably, other components of the 40S ribonucleoprotein particle were not present in the complex. hnRNP C was found to undergo significant changes of sub-nuclear localization after ionizing radiation (IR) and to partially localize to DNA damage sites. Depletion of hnRNP C substantially altered the normal balance of repair mechanisms following DSB induction, reducing HR usage in particular, and impaired S phase progression after IR. Moreover, loss of hnRNP C strongly reduced the abundance of key HR proteins BRCA1, BRCA2, RAD51 and BRIP1, which can be attributed, at least in part, to the downregulation of their mRNAs due to aberrant splicing. Our results establish hnRNP C as a key regulator of BRCA gene expression and HR-based DNA repair. They also suggest the existence of an RNA regulatory program at sites of DNA damage, which involves a unique function of hnRNP C that is independent of the 40S ribonucleoprotein particles and most other hnRNP proteins.
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