Recent advances in transcriptome analysis have revealed a large number of non-protein coding transcripts that have previously been uncharacterized. A subset of these molecules, termed long noncoding RNAs (lncRNAs), has been implicated in the regulation of chromatin states. Here, we detail a journey of lncRNA discovery and analysis, beginning from the de novo discovery of lncRNAs within the promoters of cell cycle genes, followed by the functional characterization of select candidates. We characterize two examples that regulate the p53-mediated DNA damage response. LncRNA PANDA blocks the apoptosis pathway by inhibiting the transcription factor NF-YA, and lncRNA DINO regulates the p53 transcriptional response by regulating SET7-mediated post-translational modification. Altogether, these studies support a model whereby pervasive lncRNA transcripts, previously discarded as transcriptional byproducts, function through diverse mechanisms as critical regulators of biological pathways.