 The accumulation of single-stranded DNA, SSDNA, gaps during DNA replication is associated with genotoxicity and hypersensitivity to genotoxic stress, particularly in the absence of the BRCA tumor suppressor pathway. A multi-step nucleolithic processing of SSDNA gaps converts them into cytotoxic double-stranded DNA breaks, DSBs, which are suppressed by the BRCA pathway. Exposure to environmental contaminants such as bisphenol A and diethylhexylphalate also causes SSDNA gaps, which are processed through the same mechanism to generate DSBs. This article was authored by Anastasia Hale, Ashna Dune Moon, Joshua Strocker, and others.