Processing of nonconventional DNA strand break ends

Single-strand breaks (SSBs) are one of the most common forms of genetic damage, arising from attack of DNA by reactive oxygen species or as intended or inadvertent products of normal cellular DNA metabolic events. Recent evidence linking defects in the enzymatic processing of nonconventional DNA SSBs, i.e., lesions incompatible with polymerase or ligase reactions, with inherited neurodegenerative disorders, reveals the importance of SSB repair in disease manifestation. I review herein the major eukaryotic enzymes (with an emphasis on the human proteins) responsible for the clean-up of DNA breaks harboring 3'- or 5'-blocking termini, and the cellular and disease ramifications of unrepaired SSB damage.