GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:24813610

From GONUTS
Jump to: navigation, search
Citation

Alpatov, R, Lesch, BJ, Nakamoto-Kinoshita, M, Blanco, A, Chen, S, Stützer, A, Armache, KJ, Simon, MD, Xu, C, Ali, M, Murn, J, Prisic, S, Kutateladze, TG, Vakoc, CR, Min, J, Kingston, RE, Fischle, W, Warren, ST, Page, DC and Shi, Y (2014) A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response. Cell 157:869-81

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.

Links

PubMed PMC4038154 Online version:10.1016/j.cell.2014.03.040

Keywords

Animals; Chromatin/metabolism; Chromosome Pairing; DNA Damage; Embryo, Mammalian/cytology; Fibroblasts; Fragile X Mental Retardation Protein/genetics; Fragile X Mental Retardation Protein/metabolism; Hippocampus/cytology; Histones/metabolism; Humans; Male; Meiosis; Mice; Mice, Knockout; Mutation; Neurons/metabolism; Prophase; Receptors, AMPA/metabolism; Spermatogenesis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FMR1

located_in

GO:0010369: chromocenter

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FMR1

located_in

GO:0005694: chromosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FMR1

enables

GO:0035064: methylated histone binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FMR1

involved_in

GO:0033129: positive regulation of histone phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FMR1

involved_in

GO:2001022: positive regulation of response to DNA damage stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FMR1

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

involved_in

GO:0072711: cellular response to hydroxyurea

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

involved_in

GO:0034644: cellular response to UV

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

involved_in

GO:2001022: positive regulation of response to DNA damage stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FMR1

involved_in

GO:0033129: positive regulation of histone phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FMR1

part_of

GO:0005694: chromosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FMR1

part_of

GO:0010369: chromocenter

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.