Abstract
Non-homologous end joining (NHEJ) repairs DNA double-strand breaks generated by DNA damage and also those occurring in V(D)J recombination in immunoglobulin and T cell receptor production in the immune system. In NHEJ DNA-PKcs assembles with Ku heterodimer on the DNA ends at double-strand breaks, in order to bring the broken ends together and to assemble other proteins, including DNA ligase IV (LigIV), required for DNA repair. Here we focus on structural aspects of the interactions of LigIV with XRCC4, XLF, Artemis and DNA involved in the bridging and end-joining steps of NHEJ. We begin with a discussion of the role of XLF, which interacts with Ku and forms a hetero-filament with XRCC4; this likely forms a scaffold bridging the DNA ends. We then review the well-defined interaction of XRCC4 with LigIV, and discuss the possibility of this complex interrupting the filament formation, so positioning the ligase at the correct positions close to the broken ends. We also describe the interactions of LigIV with Artemis, the nuclease that prepares the ends for ligation and also interacts with DNA-PK. Lastly we review the likely affects of Mendelian mutations on these multiprotein assemblies and their impacts on the form of inherited disease.
Highlights
Non-homologous end joining (NHEJ) is an evolutionarily conserved repair system for DNA double-strand breaks (DSBs) [1]
We focus on structural aspects of NHEJ
The DNA-PK and NHEJ ligase complexes share many common partners, for example, XLF, Ku70/80 heterodimer (Ku) and DNA itself, and contribute at DNA ends to much larger multicomponent assemblies, which vary over space and time depending on the type of DSB (Fig. 1)
Summary
Non-homologous end joining (NHEJ) is an evolutionarily conserved repair system for DNA double-strand breaks (DSBs) [1]. NHEJ and AEJ use different proteins and AEJ requires microhomology of DNA ends [2,3,4,5,6]. The core components of NHEJ are the Ku70/80 heterodimer (Ku), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4, DNA ligase IV (LigIV) and XLF/Cernunnus (XLF). Ku and DNA-PKcs together with DNA form the DNA-PK complex, and XRCC4, LigIV and XLF form the NHEJ ligase complex. The DNA-PK and NHEJ ligase complexes share many common partners, for example, XLF, Ku and DNA itself, and contribute at DNA ends to much larger multicomponent assemblies, which vary over space and time depending on the type of DSB (Fig. 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
