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., Stutzer, A., Armache, K. J., Simon, M. D., Xu, C., Ali, M., Murn, J., Prisic, S., Kutateladze, T. G., Vakoc, C. R., Min, J., Kingston, R. E., Fischle, W., Warren, S. T., Page, D. C., Shi, Y. (May 2014) A Chromatin-Dependent Role of the Fragile X Mental Retardation Protein FMRP in the DNA Damage Response. Cell, 157 (4). pp. 869-81. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/24813610
DOI: 10.1016/j.cell.2014.03.040

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
diseases & disorders > congenital hereditary genetic diseases > fragile X syndrome
diseases & disorders > congenital hereditary genetic diseases > mental retardation
CSHL Authors:
Communities: CSHL labs > Vakoc lab
Depositing User: Matt Covey
Date: 8 May 2014
Date Deposited: 15 May 2014 19:10
Last Modified: 09 Jun 2014 20:32
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30138

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