Molecules to fix genotoxic stress
RNA-binding proteins (RBPs) play a vital role in stress responses through interaction with elements within regulons, RNAs from functionally related genes. The GTOXOME (The impact of genotoxic stress on the mRNA-interactome and RNA-regulons) project has identified and characterised RBPs that are critical in the DNA damage response. Researchers found more than 40 RBPs that respond to either no stress, low DNA damage, and severe DNA damage by decreasing or increasing their RNA-binding activities. From these they isolated one novel RBP, p62. Not only is this protein completely new to the research world but it also demonstrates increased RNA-binding activity upon DNA damage and other forms of stress. The precise role of p62 was determined by the use of knock-out (ko) cells. Particularly important is its role in the G2-M DNA damage checkpoint. This checkpoint ensures mitosis does not resume until all DNA damage has been repaired after replication. Interestingly, all results point to p62 having a major role in fixing genomic instability on DSB induction. For all indicators of genomic instability tested in ko strains, the researchers found that reintroduction of p62 redressed the balance. For example, the increase in micronuclei and 53bp1 bodies in ko types after gamma-irradiation is successfully reduced after providing p62 to affected cells. GTOXOME research is pushing new boundaries and has opened new perspectives on posttranscriptional regulation after cell exposure to genotoxic stress. This should showcase the nature of cutting-edge research in the European Research Area and enhance the appeal of Europe to top-grade scientists.
Keywords
Genotoxic stress, UV, double-stranded breaks, RNA-binding proteins, DNA damage response, p62
