RT Journal Article
SR Electronic
T1 Fragile X Mental Retardation Protein regulates R-loop formation and prevents global chromosome fragility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 601906
DO 10.1101/601906
A1 Arijita Chakraborty
A1 Piroon Jenjaroenpun
A1 Andrew McCulley
A1 Jing Li
A1 Sami El Hilali
A1 Brian Haarer
A1 Elizabeth A. Hoffman
A1 Aimee Belak
A1 Audrey Thorland
A1 Heidi Hehnly
A1 Chun-long Chen
A1 Vladimir A. Kuznetsov
A1 Wenyi Feng
YR 2019
UL http://biorxiv.org/content/early/2019/06/17/601906.abstract
AB Fragile X syndrome (FXS) is the most prevalent inherited intellectual disability caused by mutations in the Fragile X Mental Retardation 1 (FMR1) gene. The protein product of FMR1, FMRP, is known as a translational repressor whose nuclear function is not understood. Here we report that FMRP is a genome maintenance protein. We show that FX cells exhibit elevated level of chromosome breaks, both spontaneous and replication stress-induced. We demonstrate that FMRP is required for abating R-loop accumulation, thereby preventing chromosome breakage. Through mapping FMRP-bound chromatin loci in normal cells and correlating with FX-specific chromosome breaks, we identified novel FXS-susceptible genes. We show that FX cells have reduced expression of the uridine diphosphoglucuronosyl transferase 1 family enzymes, suggesting defective xenobiotics glucuronidation and consequential neurotoxicity in FXS.