A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response

Roman Alpatov, Bluma J. Lesch, Mika Nakamoto-Kinoshita, Andres Blanco, Shuzhen Chen, Alexandra Stützer, Karim J. Armache, Matthew D. Simon, Chao Xu, Muzaffar Ali, Jernej Murn, Sladjana Prisic, Tatiana G. Kutateladze, Christopher R. Vakoc, Jinrong Min, Robert E. Kingston, Wolfgang Fischle, Stephen T. Warren, David C. Page, Yang Shi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it regulates translation of proteins that are important for synaptic function. We identify FMRP as a chromatin-binding protein that functions in the DNA damage response (DDR). Specifically, we show that FMRP binds chromatin through its tandem Tudor (Agenet) domain in vitro and associates with chromatin in vivo. We also demonstrate that FMRP participates in the DDR in a chromatin-binding-dependent manner. The DDR machinery is known to play important roles in developmental processes such as gametogenesis. We show that FMRP occupies meiotic chromosomes and regulates the dynamics of the DDR machinery during mouse spermatogenesis. These findings suggest that nuclear FMRP regulates genomic stability at the chromatin interface and may impact gametogenesis and some developmental aspects of fragile X syndrome.

Original languageEnglish (US)
Pages (from-to)869-881
Number of pages13
Issue number4
StatePublished - May 8 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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