Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing

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 in...

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Autores principales:	Senthil Renganathan, Subrata Pramanik, Rajasekaran Ekambaram, Arne Kutzner, Pok-Son Kim, Klaus Heese
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cell cycle centromere DNA repair proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/148914a54e2a4c2fb101d06fe3cc616a
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id	oai:doaj.org-article:148914a54e2a4c2fb101d06fe3cc616a
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spelling	oai:doaj.org-article:148914a54e2a4c2fb101d06fe3cc616a2021-11-25T17:04:57ZIdentification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing10.3390/cancers132258702072-6694https://doaj.org/article/148914a54e2a4c2fb101d06fe3cc616a2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5870https://doaj.org/toc/2072-6694Family 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.Senthil RenganathanSubrata PramanikRajasekaran EkambaramArne KutznerPok-Son KimKlaus HeeseMDPI AGarticlecell cyclecentromereDNA repairproliferationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5870, p 5870 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell cycle centromere DNA repair proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cell cycle centromere DNA repair proliferation Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Senthil Renganathan Subrata Pramanik Rajasekaran Ekambaram Arne Kutzner Pok-Son Kim Klaus Heese Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing
description	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.
format	article
author	Senthil Renganathan Subrata Pramanik Rajasekaran Ekambaram Arne Kutzner Pok-Son Kim Klaus Heese
author_facet	Senthil Renganathan Subrata Pramanik Rajasekaran Ekambaram Arne Kutzner Pok-Son Kim Klaus Heese
author_sort	Senthil Renganathan
title	Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing
title_short	Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing
title_full	Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing
title_fullStr	Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing
title_full_unstemmed	Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing
title_sort	identification of a chemotherapeutic lead molecule for the potential disruption of the fam72a-ung2 interaction to interfere with genome stability, centromere formation, and genome editing
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/148914a54e2a4c2fb101d06fe3cc616a
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Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing

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