DNA ends get exposed in cells upon either normal or dysfunctional cellular 
processes or molecular events. Telomeres need to be protected by the shelterin 
complex to avoid junctions occurring between chromosomes while failing 
topoisomerases or clustered DNA damage processing may produce double-strand 
breaks, thus requiring swift repair to avoid cell death. The rigorous study of 
the great many proteins involved in the maintenance of DNA integrity is a 
challenging task because of the innumerous unspecific electrostatic and/or 
hydrophobic DNA-protein interactions that arise due to the chemical nature of 
DNA. We devised a technique that discriminates the proteins recruited 
specifically at DNA ends from those that bind to DNA because of a generic 
affinity for the double helix. Our study shows that the DNA ends proteome 
comprises proteins of an unexpectedly wide functional spectrum, ranging from DNA 
repair to ribosome biogenesis and cytoskeleton, including novel proteins of 
undocumented function. A global mapping of the identified proteome on published 
DNA repair protein networks demonstrated the excellent specificity and 
functional coverage of our purification technique. Finally, the native 
nucleoproteic complexes that assembled specifically onto DNA ends were shown to 
be endowed with a highly efficient DNA repair activity.