Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome EditingShow others and affiliations
2021 (English)In: Cancers, ISSN 2072-6694, Vol. 13, no 22, article id 5870
Article in journal (Refereed) Published
Abstract [en]
Family with sequence similarity 72 A (FAM72A) is a pivotal mitosis-promoting factor that is highly expressed in various types of cancer. FAM72A interacts with the uracil-DNA glycosylase UNG2 to prevent mutagenesis by eliminating uracil from DNA molecules through cleaving the N-glycosylic bond and initiating the base excision repair pathway, thus maintaining genome integrity. In the present study, we determined a specific FAM72A-UNG2 heterodimer protein interaction using molecular docking and dynamics. In addition, through in silico screening, we identified withaferin B as a molecule that can specifically prevent the FAM72A-UNG2 interaction by blocking its cell signaling pathways. Our results provide an excellent basis for possible therapeutic approaches in the clinical treatment of cancer.
Place, publisher, year, edition, pages
MDPI, 2021. Vol. 13, no 22, article id 5870
Keywords [en]
DNA repair, cell cycle, centromere, proliferation
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-95663DOI: 10.3390/cancers13225870ISI: 000773917700045PubMedID: 34831023Scopus ID: 2-s2.0-85119964010OAI: oai:DiVA.org:oru-95663DiVA, id: diva2:1615009
Note
Funding agency:
National Research Foundation of Korea 2019R1F1A1056445
2021-11-292021-11-292022-04-19Bibliographically approved