The fragile X mental retardation protein FMRP plays a role in the DNA damage response

In humans, loss of the fragile X mental retardation protein, FMRP, leads to the most common inherited form of intellectual disability, the fragile X syndrome. FMRP is predominantly present in the cytoplasm where it regulates translation of proteins important for synaptic function. However a small percentage of FMRP is localized in the nucleus where its function has remained unclear. We demonstrate that FMRP associates with chromatin and participates in the replication stress-dependent DNA damage response (DDR), possibly by recognizing specific histone modifications. Taken together, our findings uncover an unexpected role of FMRP in the DDR and suggest that FMRP-dependent maintenance of genomic stability may be a potential contributing factor in the development of the fragile X syndrome.