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The fragile X mental retardation protein FMRP plays a role in the DNA damage response
Author(s) -
Shi Yang,
Alpatov Roman,
Wagner Ulrich,
Nakamoto-Kinoshita Mika,
Ye Zhen,
Luu Ying,
Armache Karim J.,
Simon Matthew D.,
Stuetzer Alexandra,
Greer Eric L.,
Wang Zhibin,
Hu Gang-Qing,
Wu Feizhen,
Xu Chao,
Beavers William N.,
Guo Yahong,
Bian Chuanbing,
Morrison Paul T.,
Vakoc Christopher R.,
Min Jinrong,
Fischle Wolfgang,
Kingston Robert E.,
Zhao Keji,
Ren Bing,
Warren Stephen T.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.88.1
Subject(s) - fragile x syndrome , chromatin , fragile x , histone , translation (biology) , fmr1 , genome instability , biology , dna damage , cytoplasm , genetics , dna replication , loss function , stress granule , function (biology) , microbiology and biotechnology , dna , gene , messenger rna , phenotype
In humans, loss of the fragile X mental retardation protein, FMRP, leads to the most common inherited form of intellectual disability, the fragile X syndrome. FMRP is predominantly present in the cytoplasm where it regulates translation of proteins important for synaptic function. However a small percentage of FMRP is localized in the nucleus where its function has remained unclear. We demonstrate that FMRP associates with chromatin and participates in the replication stress‐dependent DNA damage response (DDR), possibly by recognizing specific histone modifications. Taken together, our findings uncover an unexpected role of FMRP in the DDR and suggest that FMRP‐dependent maintenance of genomic stability may be a potential contributing factor in the development of the fragile X syndrome.