Druggable binding sites in the multicomponent assemblies that characterise DNA double-strand-break repair through non-homologous end joining
- Resource Type
- Authors
- Shikang Liang; Tom L. Blundell; Robert Appleby; Antonia Kefala Stavridi; Amanda K. Chaplin
- Source
- Essays in Biochemistry
- Subject
- DNA End-Joining Repair
Computer science
DNA repair
Druggability
Cancer therapy
Biophysics
Cell Death & Injury
Computational biology
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
therapeutics
structural biology
Humans
DNA Breaks, Double-Stranded
multicomponent systems
Protein Interaction Maps
Binding site
Molecular Biology
Review Articles
030304 developmental biology
Cancer
0303 health sciences
DNA-repair
Pharmacology & Toxicology
Double Strand Break Repair
Non-homologous end joining
enzymes and coenzymes (carbohydrates)
Structural biology
chemistry
030220 oncology & carcinogenesis
embryonic structures
DNA
- Language
Non-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.