Regulation of Fanconi anemia protein FANCD2 monoubiquitination by miR-302.
Fanconi anemia (FA) is a recessively inherited multigene disease characterized by congenital defects, progressive bone marrow failure, and heightened cancer susceptibility. Monoubiquitination of the FA pathway member FANCD2 contributes to the repair of replication stalling DNA lesions. However, cellular regulation of FANCD2 monoubiquitination remains poorly understood. In the present study, we identified the miR-302 cluster as a potential regulator of FANCD2 by bioinformatics analysis. MicroRNAs (miRNAs) are the major posttranscriptional regulators of a wide variety of biological processes, and have been implicated in a number of diseases. Expression of the exogenous miR-302 cluster (without miR-367) reduced FANCD2 monoubiquitination and nuclear foci formation. Furthermore, miR-302 cells showed extensive chromosomal breakage upon MMC treatment when compared to mock control cells. Taken together, our results suggest that overexpression of miR-302 plays a critical role in the regulation of FANCD2 monoubiquitination, resulting in characteristic defects in DNA repair within cells.
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; College of Medicine, Hanyang University, Seoul, South Korea.
Bharathi
B
Suresh
Center of Research Excellence in Corrosion, Research Institute King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia.
A Madhan
AM
Kumar
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
Hoe-Su
HS
Jeong
College of Medicine, Hanyang University, Seoul, South Korea.
Youl-Hee
YH
Cho
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; College of Medicine, Hanyang University, Seoul, South Korea. Electronic address: suresh.ramakris@gmail.com.
Suresh
S
Ramakrishna
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; College of Medicine, Hanyang University, Seoul, South Korea. Electronic address: ks66kim@hanyang.ac.kr.
Kye-Seong
KS
Kim
D045744:Cell Line, Tumor; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D054875:Ubiquitination
C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; C532169:MIRN302A microRNA, human; D035683:MicroRNAs
Chromosomal breakage; DNA repair; Fanconi anemia pathway; Monoubiquitination; Nuclear foci