ArticleMolecular cancer research : MCR2010
Functional characterization of a cancer causing mutation in human replication protein A.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- UNG-RPA interaction governs the choice between high-fidelity and mutagenic uracil repair.Nucleic acids research · 2026Article
- Review
- ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics.Nature communications · 2023Article
- Hallmarks of DNA replication stress.Molecular cell · 2022Review
- Replication Protein A Phosphorylation Facilitates RAD52-Dependent Homologous Recombination in BRCA-Deficient Cells.Molecular and cellular biology · 2022Article
- Decoding Cancer Variants of Unknown Significance for Helicase-Nuclease-RPA Complexes Orchestrating DNA Repair During Transcription and Replication.Frontiers in molecular biosciences · 2021Article
- Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair.Critical reviews in biochemistry and molecular biology · 2020Review
- The Small Bowel Cancer Incidence Enigma.Pathology oncology research : POR · 2020Review
- Radioresistance, DNA Damage and DNA Repair in Cells With Moderate Overexpression of RPA1.Frontiers in genetics · 2020Article
- Comprehensive mismatch repair gene panel identifies variants in patients with Lynch-like syndrome.Molecular genetics & genomic medicine · 2019Article
- Gene prioritization, communality analysis, networking and metabolic integrated pathway to better understand breast cancer pathogenesis.Scientific reports · 2018Article
- Interactive Roles of DNA Helicases and Translocases with the Single-Stranded DNA Binding Protein RPA in Nucleic Acid Metabolism.International journal of molecular sciences · 2017Review
- Protein dynamics of human RPA and RAD51 on ssDNA during assembly and disassembly of the RAD51 filament.Nucleic acids research · 2017Article
- DNA Damage Follows Repair Factor Depletion and Portends Genome Variation in Cancer Cells after Pore Migration.Current biology : CB · 2017Article
- The presence of extra chromosomes leads to genomic instability.Nature communications · 2016Article
- Managing Single-Stranded DNA during Replication Stress in Fission Yeast.Biomolecules · 2015Review
- Replication protein A prevents promiscuous annealing between short sequence homologies: Implications for genome integrity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- Chemical inhibitor targeting the replication protein A-DNA interaction increases the efficacy of Pt-based chemotherapy in lung and ovarian cancer.Biochemical pharmacology · 2015Article
- Replication protein A: single-stranded DNA's first responder: dynamic DNA-interactions allow replication protein A to direct single-strand DNA intermediates into different pathways for synthesis or repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Replication protein A (RPA) is the primary ssDNA-binding protein in eukaryotes. RPA is essential for DNA replication, repair, and recombination. Mutation of a conserved leucine residue to proline in the high-affinity DNA binding site of RPA (residue L221 in human RPA) has been shown to have defects in DNA repair and a high rate of chromosomal rearrangements in yeast. The homologous mutation in mice was found to be lethal when homozygous and to cause high rates of cancer when heterozygous. To understand the molecular defect causing these phenotypes, we created the homologous mutation in the human RPA1 gene (L221P) and analyzed its properties in cells and in vitro. RPA1(L221P) does not support cell cycle progression when it is the only form of RPA1 in HeLa cells. This phenotype is caused by defects in DNA replication and repair. No phenotype is observed when cells contain both wild-type and L221P forms of RPA1, indicating that L221P is not dominant. Recombinant L221P polypeptide forms a stable complex with the other subunits of RPA, indicating that the mutation does not destabilize the protein; however, the resulting complex has dramatically reduced ssDNA binding activity and cannot support SV40 DNA replication in vitro. These findings indicate that in mammals, the L221P mutation causes a defect in ssDNA binding and a nonfunctional protein complex. This suggests that haploinsufficiency of RPA causes an increase in the levels of DNA damage and in the incidence of cancer.
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Registered trials
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