A Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response
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Author(s)
Alpatov, Roman
Nakamoto-Kinoshita, Mika
Blanco, Andres
Chen, Shuzhen
Stützer, Alexandra
Armache, Karim J.
Simon, Matthew D.
Xu, Chao
Ali, Muzaffar
Murn, Jernej
Date Issued
May 2014
Journal
Cell
Publisher
Elsevier
Citation
Alpatov, Roman et al. “A Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response.” Cell 157.4 (2014): 869–881.
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Author's final manuscript
Abstract
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.
MIT Department
Howard Hughes Medical Institute
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2014.03.040
