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
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: | 16 Jul 2021 16:01 |
| PMCID: | PMC4038154 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30138 |
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