Functional Investigation of the Novel BRCA1variant (Glu1661Gly) by Computational Tools and Yeast Transcription Activation Assay

Q: How can I download an article?

To download an article from SID, first log in to the site, search for the article title, and click on the 'Download Article' option.

Q: How can I download an ISI article?

To download an ISI article on SID, enter the keyword or article title in the search bar, view the relevant results, click on the desired article, and select the 'Download Article' option.

Q: How can I access the SID database?

To access the SID database, visit SID.ir, create an account, and log in to access scientific resources.

Q: Is downloading articles from SID free?

Some articles on SID are available for free, while others require payment. Details are specified on the article's page.

Yadegari Fatemeh; FARAHMAND LEILA; ESMAEILI REZVAN; Zarinfam Shiva; MAJIDZADEH A. KEIVAN

مرکز اطلاعات علمی Scientific Information Database (SID) - Trusted Source for Research and Academic Resources

Journal Paper

Paper Information

Journal: MULTIDISCIPLINARY CANCER INVESTIGATION Year:2019 | Volume:3 | Issue:2 Page(s): 20-26

Download Full-Text

View:

230

Download:

147

Cites:

Information Journal Paper

Title

Functional Investigation of the Novel BRCA1variant (Glu1661Gly) by Computational Tools and Yeast Transcription Activation Assay

Author(s)

Keywords

Susceptibility Genes

BRCA1

VUS

Hereditary Breast and Ovarian Cancer Syndrome

Transcriptional Activation

Abstract

Introduction: Mutations in the BRCA1 gene are major risk factors for breast and ovarian cancers. However, the relationship between some BRCA1 mutations and cancer risk remains largely unknown. Cancer risk predictions could be improved by evaluation of the impairment degree in the BRCA1 functions due to a specific mutation. This study aimed to assess the functional effect of a novel variant (Glu1661Gly) in BRCA1 gene by a combination of in silico tools, structural analysis, and also experimental functional assay based on yeast transcription activation. Methods: Computational tools including PROVEAN, PolyPhen2, Align-GVGD, Mutation Taster, and also structural analysis were used for prediction of the impact of Glu1661Gly on protein function. To perform the yeast functional assay, the BRCA1 C-terminal (BRCT domain) was cloned into pLexA plasmid in-frame with the DNA-binding domain of LexA to generate a functional transcription activator. The resulted construct was transformed into EGY48/ pRB1840 yeast and positive colonies were assayed for β-galactosidase activity. Wild-type BRCA1 and Ser1613Gly were used as positive controls and Met1775Arg as negative control. Results: The Glu1661Gly variant was predicted to be neutral by PROVEAN, diseasecausing by Mutation Taster, probably damaging by Polyphen2, and intermediate effect by Align-GVGD. The yeast functional assay revealed that Glu1661Gly activity was comparable to wild-type BRCA1. Conclusions: Observed discrepancies between in silico tools make it difficult to interpret the results. Based on structural analysis, the Glu1661Gly on α 1 helix of the C-terminal domain does not seem to impair function due to α 1 helix is far from the BRCT-BRCT interface and phosphopeptide-binding site. This variant was also classified as neutral; using yeast functional assay.

Multimedia

No record.

Cites

No record.

References

Mutational spectrum in a worldwide study of 29, 700 families with BRCA1 or BRCA2 mutations

Cite

APA: Copy

Yadegari, Fatemeh, FARAHMAND, LEILA, ESMAEILI, REZVAN, Zarinfam, Shiva, & MAJIDZADEH A., KEIVAN. (2019). Functional Investigation of the Novel BRCA1variant (Glu1661Gly) by Computational Tools and Yeast Transcription Activation Assay. MULTIDISCIPLINARY CANCER INVESTIGATION, 3(2), 20-26. SID. https://sid.ir/paper/349720/en

Vancouver: Copy

Yadegari Fatemeh, FARAHMAND LEILA, ESMAEILI REZVAN, Zarinfam Shiva, MAJIDZADEH A. KEIVAN. Functional Investigation of the Novel BRCA1variant (Glu1661Gly) by Computational Tools and Yeast Transcription Activation Assay. MULTIDISCIPLINARY CANCER INVESTIGATION[Internet]. 2019;3(2):20-26. Available from: https://sid.ir/paper/349720/en

IEEE: Copy

Fatemeh Yadegari, LEILA FARAHMAND, REZVAN ESMAEILI, Shiva Zarinfam, and KEIVAN MAJIDZADEH A., “Functional Investigation of the Novel BRCA1variant (Glu1661Gly) by Computational Tools and Yeast Transcription Activation Assay,” MULTIDISCIPLINARY CANCER INVESTIGATION, vol. 3, no. 2, pp. 20–26, 2019, [Online]. Available: https://sid.ir/paper/349720/en

Related Journal Papers

No record.

Related Seminar Papers

No record.

Related Plans

No record.

Recommended Workshops