2012•The FASEB JournalRequires access
The fragile X mental retardation protein FMRP plays a role in the DNA damage response
Yang Shi, Roman Alpatov, Ulrich Wagner, Mika Nakamoto-Kinoshita, Zhen Ye, Ying Luu, Karim J. Armache, Matthew D. Simon, Alexandra Stüetzer, Eric Lieberman Greer, Zhibin Wang, Gangqing Hu, Feizhen Wu, Chao Xu, William N. Beavers, Yahong Guo, Chuanbing Bian, Paul T. Morrison, Christopher R. Vakoc, Jinrong Min, Wolfgang Fischle, Robert E. Kingston, Keji Zhao, Bing Ren, Stephen T. Warren
Open publisher page 2 citations
Abstract
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.