p53 cooperates with DNA methylation and interferon response to maintain silencing of repeats and noncoding RNA. The study found that loss of p53 and DNA methylation leads to transcription of repeats like SINEs and satellite DNA. This massive transcription activates an antiviral interferon response in p53-null cells, causing cell death. The model suggests p53, DNA methylation, and interferon response cooperate to epigenetically silence repeats and prevent genomic instability.