Abstract
DNA double-strand breaks (DSBs) are accidental lesions generated by various endogenous or exogenous stresses. DSBs are also genetically programmed events during the V(D)J recombination process, meiosis, or other genome rearrangements, and they are intentionally generated to kill cancer during chemo- and radiotherapy. Most DSBs are processed in mammalian cells by the classical nonhomologous end-joining (c-NHEJ) pathway. Understanding the molecular basis of c-NHEJ has major outcomes in several fields, including radiobiology, cancer therapy, immune disease, and genome editing. The heterodimer Ku70/80 (Ku) is a central actor of the c-NHEJ as it rapidly recognizes broken DNA ends in the cell and protects them from nuclease activity. It subsequently recruits many c-NHEJ effectors, including nucleases, polymerases, and the DNA ligase 4 complex. Beyond its DNA repair function, Ku is also involved in several other DNA metabolism processes. Here, we review the structural and functional data on the DNA and RNA recognition properties of Ku implicated in DNA repair and in telomeres maintenance.
Highlights
Living organisms are constantly exposed to genotoxic stress that can lead to doublestrand breaks (DSBs)
We mainly focus on the molecular basis of the interactions of Ku with various DNA ends observed during DSB formation and on its interactions with RNA and DNA substrates at telomeres
HeLa extracts by immunoabsorbent column chromatography, they showed that Ku binds double-strand DNA more efficiently than single-strand DNA, and they identified an interaction with dsDNA that is salt-dependent
Summary
Living organisms are constantly exposed to genotoxic stress that can lead to doublestrand breaks (DSBs). The heterodimer Ku70/80 (called Ku hereafter) is a central actor of the c-NHEJ pathway It is considered as one of the first factors to be recruited at DSB sites because of its high affinity for DNA ends (Kd in the nM range) and its high abundance in the nucleus [5]. HeLa extracts by immunoabsorbent column chromatography, they showed that Ku binds double-strand DNA (dsDNA) more efficiently than single-strand DNA (ssDNA), and they identified an interaction with dsDNA that is salt-dependent. They reported that Ku efficiently binds a linearized plasmid but not the circular form. The authors made the hypothesis that Ku may be “associated with DNA break points that might occur through the action of such agents as UV light or certain drugs” and have a role in DNA damage repair
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