Ultraviolet irradiation resistance-associated gene (UVRAG) is a tumour suppressor gene known to activate autophagy. Here, Zhao et al. identify an autophagy-independent role for UVRAG in chromosomal stability. First, UVRAG was shown to interact with the DNA-dependent protein kinase (DNA–PK) complex, which has a central role in the non-homologous end joining (NHEJ) pathway of DNA repair. Interestingly, this interaction was found to promote double-strand break repair in an autophagy-independent manner. Second, the authors observed that UVRAG is targeted to the centrosome by centrosome protein 63. Association of UVRAG with the centrosome was required for centrosome stability and correct chromosome segregation. Thus, the authors propose that the ternary role of UVRAG in autophagy, DNA repair and centrosome stability may explain why it is frequently mutated in cancers.
ORIGINAL RESEARCH PAPER
Zhao, Z. et al. A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. Dev. Cell 26 Apr 2012 (doi:10.1016/j.devcel.2011.12.027)
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Papatriantafyllou, M. An autophagy-independent role for UVRAG. Nat Rev Mol Cell Biol 13, 340 (2012). https://doi.org/10.1038/nrm3366
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DOI: https://doi.org/10.1038/nrm3366