TY - JOUR T1 - SMN-deficient cells exhibit increased ribosomal DNA damage JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101145 VL - 5 IS - 8 SP - e202101145 AU - Evangelia Karyka AU - Nelly Berrueta Ramirez AU - Christopher P Webster AU - Paolo M Marchi AU - Emily J Graves AU - Vinay K Godena AU - Lara Marrone AU - Anushka Bhargava AU - Swagat Ray AU - Ke Ning AU - Hannah Crane AU - Guillaume M Hautbergue AU - Sherif F El-Khamisy AU - Mimoun Azzouz Y1 - 2022/08/01 UR - https://www.life-science-alliance.org/content/5/8/e202101145.abstract N2 - Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity. DNA damage and genome instability have been linked to a range of neurodegenerative diseases. The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. Instability in rDNA has been associated with cancer, premature ageing syndromes, and a number of neurodegenerative disorders. Here, we report that SMN-deficient cells exhibit increased rDNA damage leading to impaired ribosomal RNA synthesis and translation. We also unravel an interaction between SMN and RNA polymerase I. Moreover, we uncover an spinal muscular atrophy motor neuron-specific deficiency of DDX21 protein, which is required for resolving R-loops in the nucleolus. Taken together, our findings suggest a new role of SMN in rDNA integrity. ER -