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

Alpatov, R., Lesch, B. J., Nakamoto-Kinoshita, M., Blanco, A., Chen, S., Stützer, A., et al. (2014). A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response. Cell, 157(4), 869-881. doi:10.1016/j.cell.2014.03.040.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-B67F-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CB21-6
Genre: Journal Article

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 Creators:
Alpatov, R., Author
Lesch, B. J., Author
Nakamoto-Kinoshita, M., Author
Blanco, A., Author
Chen, S., Author
Stützer, A.1, Author              
Armache, K. J., Author
Simon, M. D., Author
Xu, C., Author
Ali, M., Author
Murn, J., Author
Prisic, S., Author
Kutateladze, T. G., Author
Vakoc, C. R., Author
Min, J., Author
Kingston, R. E., Author
Fischle, W.1, Author              
Warren, S. T., Author
Page, D. C., Author
Shi, Y., Author
Affiliations:
1Research Group of Chromatin Biochemistry, MPI for biochemical chemistry, Max Planck Society, ou_578604              

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 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.

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Language(s): eng - English
 Dates: 2014-05-08
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.cell.2014.03.040
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 157 (4) Sequence Number: - Start / End Page: 869 - 881 Identifier: -