Death inducer obliterator protein 1 in the context of DNA regulation -: Sequence analyses of distant homologues point to a novel functional role

Death inducer obliterator protein 1 [DIDO1; also termed DIO-1 and death-associated transcription factor 1 (DATF-1)] is encoded by a gene thus far described only in higher vertebrates. Current gene ontology descriptions for this gene assign its function to an apoptosis-related process. The protein presents distinct splice variants and is distributed ubiquitously. Exhaustive sequence analyses of all DIDO variants identify distant homologues in yeast and other organisms. These homologues have a role in DNA regulation and chromatin stability, and form part of higher complexes linked to active chromatin. Further domain composition analyses performed in the context of related homologues suggest that DIDO-induced apoptosis is a secondary effect. Gene-targeted mice show alterations that include lagging chromosomes, and overexpression of the gene generates asymmetric nuclear divisions. Here we describe the analysis of these eukaryote-restricted proteins and propose a novel, DNA regulatory function for the DIDO protein in mammals.