The Double Face of Base Excision Repair: Preventing and Triggering Double-Strand Breaks.

How cells repair oxidative damage to DNA has been studied for over 60 years. Recent evidence confirms that the base excision repair (BER) machinery not only acts to restore an intact double DNA helix by replacing oxidized bases, but under some circumstances, BER goes awry, generating double-strand breaks and provoking chromosome fragmentation. This fragmentation can lead to extensive genomic rearrangements that correlate with oncogenesis. Whether the BER factors suppress or promote DNA damage depends on multiple parameters: the nature of the damage, the clustering of modified bases, the pathway of BER chosen, and chromatin remodelers. Recent data leading to this unexpected role for BER are reviewed here.