Many standard of care chemotherapeutic agents exert their effects by causing DNA damage. In response to DNA damage, cells activate the DNA-damage response-signaling network to arrest the cell cycle and initiate DNA repair. Proteins involved in RNA processing and stability constitute the largest single class of proteins that modulate the DNA damage response and comprise a very large number of the identified substrates for the ATR/Chk1, ATM/Chk2, DNA-PK, and p38MAPK/MK2 DNA damage-activated protein kinase pathways. Recent work from our laboratory implicates RNA-binding proteins, as key molecular integrators that control the cellular response to DNA damaging agents. We are using state-of-the-art techniques to understand this link between DNA damage-activated signaling pathways and global control of gene expression at the posttranscriptional level leading to the development of chemotherapy resistance through the action of RNA-binding proteins.
The RNA-binding protein hnRNPA0 controls distinct cell cycle checkpoints to drive resistance of p53-defective tumors to chemotherapy (Cannell et al, Cancer Cell, 2015)