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http://purl.uniprot.org/citations/18413724http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18413724http://www.w3.org/2000/01/rdf-schema#comment"BCR/ABL kinase-positive chronic myelogenous leukemia (CML) cells display genomic instability leading to point mutations in various genes including bcr/abl and p53, eventually causing resistance to imatinib and malignant progression of the disease. Mismatch repair (MMR) is responsible for detecting misincorporated nucleotides, resulting in excision repair before point mutations occur and/or induction of apoptosis to avoid propagation of cells carrying excessive DNA lesions. To assess MMR activity in CML, we used an in vivo assay using the plasmid substrate containing enhanced green fluorescent protein (EGFP) gene corrupted by T:G mismatch in the start codon; therefore, MMR restores EGFP expression. The efficacy of MMR was reduced approximately 2-fold in BCR/ABL-positive cell lines and CD34(+) CML cells compared with normal counterparts. MMR was also challenged by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which generates O(6)-methylguanine and O(4)-methylthymine recognized by MMR system. Impaired MMR activity in leukemia cells was associated with better survival, accumulation of p53 but not of p73, and lack of activation of caspase 3 after MNNG treatment. In contrast, parental cells displayed accumulation of p53, p73, and activation of caspase 3, resulting in cell death. Ouabain-resistance test detecting mutations in the Na(+)/K(+) ATPase was used to investigate the effect of BCR/ABL kinase-mediated inhibition of MMR on mutagenesis. BCR/ABL-positive cells surviving the treatment with MNNG displayed approximately 15-fold higher mutation frequency than parental counterparts and predominantly G:C-->A:T and A:T-->G:C mutator phenotype typical for MNNG-induced unrepaired lesions. In conclusion, these results suggest that BCR/ABL kinase abrogates MMR activity to inhibit apoptosis and induce mutator phenotype."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.org/dc/terms/identifier"doi:10.1158/0008-5472.can-07-6858"xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Herrera L."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Skorski T."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Nieborowska-Skorska M."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Slupianek A."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Blasiak J."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Stoklosa T."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Koptyra M."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Poplawski T."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Seferynska I."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Basak G."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/author"Rayevskaya M."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/name"Cancer Res"xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/pages"2576-2580"xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/title"BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutations."xsd:string
http://purl.uniprot.org/citations/18413724http://purl.uniprot.org/core/volume"68"xsd:string
http://purl.uniprot.org/citations/18413724http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18413724
http://purl.uniprot.org/citations/18413724http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18413724
http://purl.uniprot.org/uniprot/#_A0A023PX70-mappedCitation-18413724http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18413724
http://purl.uniprot.org/uniprot/#_A0A510LHF0-mappedCitation-18413724http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18413724
http://purl.uniprot.org/uniprot/#_A0A510LHH1-mappedCitation-18413724http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18413724
http://purl.uniprot.org/uniprot/#_A0A510LIH5-mappedCitation-18413724http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/18413724