| تعداد نشریات | 24 |
| تعداد شمارهها | 903 |
| تعداد مقالات | 8,081 |
| تعداد مشاهده مقاله | 15,203,607 |
| تعداد دریافت فایل اصل مقاله | 12,847,933 |
Functional investigation of the BRCA1 Val1714Gly and Asp1733Gly variants by computational tools and yeast transcription activation assay | ||
| Molecular Biology Research Communications | ||
| مقاله 3، دوره 8، شماره 3، 2019، صفحه 113-118 اصل مقاله (304.94 K) | ||
| نوع مقاله: Original article | ||
| شناسه دیجیتال (DOI): 10.22099/mbrc.2019.33971.1414 | ||
| نویسندگان | ||
| Fatemeh Yadegari1؛ Leila Farahmand2؛ Rezvan Esmaeili1؛ Tannaz Samadi1؛ Keivan Majidzadeh* 1 | ||
| 1Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran | ||
| 2Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran | ||
| چکیده | ||
| Mutations in the BRCA1 gene are known to be a major cause of hereditary breast cancer. However, characterizing the point mutationsassociated with cancer in BRCA1 is challenging because the functional impact of most of them is still unknown. Nowadays, a variety of methods are employed to identify cancer-associated mutations in BRCA1. This study is aimed to assess the functional effects of two mutations, Asp1733Gly and Val1714Gly, using a combination of in silico tools and yeast functional transcription activator assay. Our computational analysis showed that theVal1714Gly mutation was deleterious, while the other one, Asp1733Gly, predicted as neutral. Also using yeast functional transcription activator assay, we found that the Asp1733Gly mutation displayed similar ability with positive controls. In contrast, the Val1714Gly mutation completely abrogated transcriptional activity in the yeast. These results suggested that Val1714Gly and Asp1733Gly can be classified as pathogenic and benign mutations for the BRCA1, respectively. | ||
| کلیدواژهها | ||
| BRCA1؛ in silico tools؛ Functional assay؛ Yeast | ||
| مراجع | ||
|
1. Friedman LS, Ostermeyer EA, Szabo CI, Dowd P, Lynch ED, Rowell SE, King MC. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nat Genet 1994;8:399-404. 2. Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, Seal S, Hamoudi R, van Rensburg EJ, Dunning AM, Love R, Evans G, Easton D, Clayton D, Stratton MR, Ponder BA. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation. Nat Genet 1995;11:428-433. 3. Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE. Structure of a BRCA1-BARD1 heterodimeric RING–RING complex. Nat Struct Biol 2001;8:833-837. 4. Shen D,Vadgama JV. BRCA1 and BRCA2 gene mutation analysis: visit to the breast cancer information core (BIC). Oncol Res 1999;11:63-69. 5. Pires AS, Porto WF, Franco OL, Alencar SA. In silico analyses of deleterious missense SNPs of human apolipoprotein E3. Sci Rep 2017;7:2509. 6. George DC, Chakraborty C, Haneef SA, NagaSundaram N, Chen L, Zhu H. Evolution-and structure-based computational strategy reveals the impact of deleterious missense mutations on MODY-2 (maturity-onset diabetes of the young, type 2). Theranostics 2014;4:366-385. 7. Humphrey JS, Salim A, Erdos MR, Collins FS, Brody LC, Klausner RD. Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing. Proc Natl Acad Sci USA 1997; 94:5820-5825. 8. Chapman MS,Verma IM. Transcriptional activation by BRCAl. Nature 1996;382:678-679. 9. Monteiro AN, August A, Hanafusa H. Evidence for a transcriptional activation function of BRCA1 C-terminal region. Proc Natl Acad Sci USA 1996;93:13595-13599. 10. Carvalho MA, Couch FJ, Monteiro AN. Functional assays for BRCA1 and BRCA2. Int J Biochem Cell Biol 2007;39:298-310. 11. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994;266:66-71. 12. Abel KJ, Xu J, Yin GY, Lyons RH, Meisler MH, Weber BL. Mouse Brca1: localization, sequence analysis and identification of evolutionarily conserved domains. Hum MolGenet 1995;4:2265-2273. 13. Vallon-Christersson J, Cayanan C, Haraldsson K, Loman N, Bergthorsson JT, Brøndum-Nielsen K, Gerdes AM, Møller Pl, Kristoffersson U, Olsson H, Borg A,Monteiro AN Functional analysis of BRCA1 C-terminal missense mutations identified in breast and ovarian cancer families. Hum Mol Genet 2001;10:353-360. 14. Carvalho MA, Marsillac SM, Karchin R, Manoukian S, Grist S, Swaby RF, Urmenyi TP, Rondinelli E, Silva R, Gayol L, Baumbach L, Sutphen R, Pickard-Brzosowicz JL, Nathanson KL, Sali A, Goldgar D, Couch FJ, Radice P, Monteiro AN. Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis. Cancer Res 2007;67:1494-1501. 15. Lee MS, Green R, Marsillac SM, Coquelle N, Williams RS, Yeung T, Foo D, Hau DD, Hui B, Monteiro AN, Glover JN. Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. Cancer Res2010;70:4880-4890. 16. Oosthuizen J. Molecular screening of Coloured South African breast cancer patients for the presence of BRCA mutations using high resolution melting analysisIn Faculty of Health Sciences 2016, University of the Free State: Bloemfontein, South Africa. 17. Judkins T, Hendrickson BC, Deffenbaugh AM, Eliason K, Leclair B, Norton MJ, Ward BE, Pruss D, Scholl T. Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. Cancer Res 2005;65:10096-10103. 18. Tavtigian SV, Deffenbaugh AM, Yin L, Judkins T, Scholl T, Samollow PB, de Silva D, Zharkikh A, Thomas A. Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. J Med Genet 2006; 43:295-305. 19. Mathe E, Olivier M, Kato S, Ishioka C, Hainaut P, Tavtigian SV. Computational approaches for predicting the biological effect of p53 missense mutations: a comparison of three sequence analysis based methods. Nucleic Acids Res 2006;34:1317-1325. 20. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009;4:1073-1081. 21. Schwarz JM, Rödelsperger C, Schuelke M, Seelow D. MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods 2010;7:575-576. 22. Chun S, Fay JC. Identification of deleterious mutations within three human genomes. Genome Res 2009;19:1553-1561. 23. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 1989;77:51-59. 24. Hayes F, Cayanan C, Barillà D, Monteiro AN. Functional assay for BRCA1: mutagenesis of the COOH-terminal region reveals critical residues for transcription activation. Cancer Res 2000;60:2411-2418. 25. Golemis E,Gyuris J. Two-hybrid system/interaction traps Ausubel FM Brent R. Kingston R. Moore D. Seidman J. Smith JA Struhl K. eds. Current Protocols in Molecular Biology 1994; 13:1-13.14. 26. Estojak J, Brent R, Golemis EA. Correlation of two-hybrid affinity data with in vitro measurements. Mol Cell Biol 1995;15:5820-5829. 27. Brent R, Ptashne M. A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor. Cell 1985;43:729-736. 28. Monteiro AN, August A, Hanafusa H. Common BRCA1 variants and transcriptional activation. Am J Hum Genet 1997;61:761-762. | ||
|
آمار تعداد مشاهده مقاله: 1,611 تعداد دریافت فایل اصل مقاله: 1,346 |
||