Hypoxia also switches DNA damage response pathway coding transcripts to non-coding intron-retained alternative spliced transcripts in genes, such as HDAC6, a cytotoxic response regulator that regulates inhibitory alternative splicing of the TP53BP1 p53 binding protein and TP53 co-factor, resulting in de-regulated double strand DNA repair in colorectal cancers, highlighting a predominant role for hypoxia-induced alternative splicing in de-regulating the DNA damage and DNA repair responses (Fig. 5b )[118]. The gene discussed is TP53; the disease is colorectal cancer.