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- _6 label "Selventa" provenance.
- large_corpus.bel rights "Copyright (c) 2011-2012, Selventa. All rights reserved." provenance.
- _5 value "Replication protein A (RPA) is a 3-subunit single-stranded DNA (ssDNA)-binding protein that has been isolated from human cells and found to be essential for in vitro replication of the papovavirus SV40. Erdile et al. (1991) reported the sequence of a cDNA encoding the 70-kD subunit. The human cDNA directed production in E. coli of a 70-kD protein that reacted with a monoclonal antibody directed against the 70-kD subunit of the human protein. The recombinant subunit, purified from bacteria, exhibited single-stranded DNA-binding activity comparable to that of the complete RPA complex. It could substitute for the complete complex in stimulating the activity of DNA polymerase alpha-primase, but could not substitute for the complete complex in SV40 DNA replication in vitro, suggesting an important functional role for the other subunits. GENE FUNCTION Gomes and Wold (1996) constructed a series of N-terminal deletions of RPA70 to explore the function of the protein. Their data indicated that RPA70 is composed of 3 functional domains: an N-terminal domain that is not required for single-stranded DNA binding or SV40 replication, a central DNA-binding domain, and a C-terminal domain that is essential for subunit interactions. The folding of mRNA influences a diverse range of biologic events such as mRNA splicing and processing and translational control and regulation. Because the structure of mRNA is determined by its nucleotide sequence and its environment, Shen et al. (1999) examined whether the folding of mRNA could be influenced by the presence of single-nucleotide polymorphisms (SNPs). They reported marked differences in mRNA secondary structure associated with SNPs in the coding region of 2 human mRNAs: alanyl-tRNA synthetase (601065) and replication protein A, 70-kD subunit. Enzymatic probing of SNP-containing fragments of the mRNAs revealed pronounced allelic differences in cleavage pattern at sites 14 or 18 nucleotides away from the SNP, suggesting that a single-nucleotide variation can give rise to different mRNA folds. By using oligodeoxyribonucleotides complementary to the region of different allelic structures in the RPA70 mRNA, but not extending to the SNP itself, they found that the SNP exerted an allele-specific effect on the accessibility of its flanking site in the endogenous human RPA70 mRNA. The results demonstrated the contribution of common genetic variation through structural diversity of mRNA and suggested a broader role than previously thought for the effects of SNPs on mRNA structure and, ultimately, biologic function. Nakayama et al. (1999) reported that a -786T-C mutation (163729.0002), in the promoter region of the endothelial nitric oxide synthase (eNOS) gene reduced transcription of the gene and was strongly associated with coronary spastic angina and myocardial infarction. Miyamoto et al. (2000) determined that RPA1 specifically binds to the mutant allele in nuclear extracts from HeLa cells. In human umbilical vein endothelial cells, inhibition of RPA1 expression using antisense oligonucleotides restored transcription driven by the mutated promoter sequence, whereas overexpression of RPA1 further reduced it. Serum nitrite-nitrate levels among individuals carrying the -786T-C mutation were significantly lower than among those without the mutation. The authors concluded that RPA1 apparently functions as a repressor protein in the -786T-C mutation-related reduction of eNOS gene transcription associated with the development of coronary artery disease. The function of the ATR (601215)-ATRIP (606605) protein kinase complex is crucial for the cellular response to replication stress and DNA damage. Zou and Elledge (2003) demonstrated that the RPA complex, which associates with single-stranded DNA, is required for recruitment of ATR to sites of DNA damage and for ATR-mediated CHK1 (603078) activation in human cells. In vitro, RPA stimulates the binding of ..." provenance.
- _5 wasQuotedFrom _4 provenance.
- assertion hadPrimarySource _4 provenance.
- large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
- _4 title "RPA1 omim" provenance.
- large_corpus.bel description "Approximately 61,000 statements." provenance.
- assertion wasDerivedFrom large_corpus.bel provenance.
- assertion wasDerivedFrom _5 provenance.
- large_corpus.bel authoredBy _6 provenance.
- large_corpus.bel version "20131211" provenance.
- _4 identifier "RPA1 omim" provenance.
- _4 type "Online Resource" provenance.