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Article: Druggable binding sites in the multicomponent assemblies that characterise DNA double-strand-break repair through non-homologous end joining

TitleDruggable binding sites in the multicomponent assemblies that characterise DNA double-strand-break repair through non-homologous end joining
Authors
Issue Date2020
Citation
Essays in Biochemistry, 2020, v. 64, n. 5, p. 791-806 How to Cite?
AbstractNon-homologous end joining (NHEJ) is one of the two principal damage repair pathways for DNA double-strand breaks in cells. In this review, we give a brief overview of the system including a discussion of the effects of deregulation of NHEJ components in carcinogenesis and resistance to cancer therapy. We then discuss the relevance of targeting NHEJ components pharmacologically as a potential cancer therapy and review previous approaches to orthosteric regulation of NHEJ factors. Given the limited success of previous investigations to develop inhibitors against individual components, we give a brief discussion of the recent advances in computational and structural biology that allow us to explore different targets, with a particular focus on modulating protein-protein interaction interfaces. We illustrate this discussion with three examples showcasing some current approaches to developing protein-protein interaction inhibitors to modulate the assembly of NHEJ multiprotein complexes in space and time.
Persistent Identifierhttp://hdl.handle.net/10722/336249
ISSN
2023 Impact Factor: 5.6
2023 SCImago Journal Rankings: 1.841
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorStavridi, Antonia Kefala-
dc.contributor.authorAppleby, Robert-
dc.contributor.authorLiang, Shikang-
dc.contributor.authorBlundell, Tom L.-
dc.contributor.authorChaplin, Amanda K.-
dc.date.accessioned2024-01-15T08:24:52Z-
dc.date.available2024-01-15T08:24:52Z-
dc.date.issued2020-
dc.identifier.citationEssays in Biochemistry, 2020, v. 64, n. 5, p. 791-806-
dc.identifier.issn0071-1365-
dc.identifier.urihttp://hdl.handle.net/10722/336249-
dc.description.abstractNon-homologous end joining (NHEJ) is one of the two principal damage repair pathways for DNA double-strand breaks in cells. In this review, we give a brief overview of the system including a discussion of the effects of deregulation of NHEJ components in carcinogenesis and resistance to cancer therapy. We then discuss the relevance of targeting NHEJ components pharmacologically as a potential cancer therapy and review previous approaches to orthosteric regulation of NHEJ factors. Given the limited success of previous investigations to develop inhibitors against individual components, we give a brief discussion of the recent advances in computational and structural biology that allow us to explore different targets, with a particular focus on modulating protein-protein interaction interfaces. We illustrate this discussion with three examples showcasing some current approaches to developing protein-protein interaction inhibitors to modulate the assembly of NHEJ multiprotein complexes in space and time.-
dc.languageeng-
dc.relation.ispartofEssays in Biochemistry-
dc.titleDruggable binding sites in the multicomponent assemblies that characterise DNA double-strand-break repair through non-homologous end joining-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1042/EBC20190092-
dc.identifier.pmid32579168-
dc.identifier.scopuseid_2-s2.0-85090662907-
dc.identifier.volume64-
dc.identifier.issue5-
dc.identifier.spage791-
dc.identifier.epage806-
dc.identifier.isiWOS:000611913500009-

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