hnRNPs also play a role in DNA damage response in coordination with p53. hnRNP K is rapidly induced after DNA damage by ionizing radiation. It cooperates with p53 to induce the activation of p53 target genes, thus activating cell-cycle checkpoints.  p53 itself is an important tumor-suppressor gene sometimes known by the epithet “the guardian of the genome.” hnRNP K’s close association with p53 demonstrates its importance in DNA damage control.
p53 regulates a large group of RNAs that are not translated into protein, called large intergenic noncoding RNAs (lincRNAs). p53 suppression of genes is often carried out by a number of these lincRNAs, which in turn have been shown to act though hnRNP K. Through physical interactions with these molecules, hnRNP K is targeted to genes and transmits p53 regulation, thus acting as a key repressor within the p53-dependent transcriptional pathway.