The Institute of Genetic Development and others found that fragile X mental retardation protein FMRP is involved in the mechanism of DNA damage response

Fragile X syndrome is the most common inherited mental defect in the world. It is caused by the functional defect of Fragile X mental retardation protein (FMRP), but its pathogenic mechanism is still rarely caused. The research team of Zhang Yongqing, the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and the research team of Professor Mi Xiaolin from the Cancer Stem Cell Research Institute of Dalian Medical University worked closely to discover the mechanism by which FMRP participates in regulating the DNA damage response.

Using the classic model organism Drosophila, the researchers found that the mutant Drosophila is highly sensitive to γ-rays and chemical mutagens. FMRP-deficient Drosophila showed G2 / M cell cycle checkpoint defects caused by DNA damage. This defect was caused by the abnormally increased expression of CycB in FMRP-deficient Drosophila. CycB is one of the key factors that regulate the entry of cells into the mitotic phase. Studies have found that FMRP can bind to CycB mRNA, inhibit the expression of CycB protein, and thus participate in the regulation of the cell cycle. In addition, FMRP-deficient Drosophila showed a significant increase in p53-dependent apoptosis induced by radiation.

This study reveals for the first time that FMRP protein participates in DNA damage response, expanding people's understanding of DNA damage response mechanism. At the same time, it also deepens the understanding of the pathogenesis of fragile X syndrome and provides new ideas for the diagnosis and treatment of fragile X syndrome.

The results of this study were published online in the Journal of Human Molecular Genetics (DOI: 10.1093 / hmg / dds307) on July 26. Dr. Wei Liu from the researcher lab of Zhang Yongqing was the first author of the paper.

The research work was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology and the Chinese Academy of Sciences.