RT Journal Article SR Electronic T1 Nol12 is a multifunctional endonuclease at the nexus of RNA and DNA metabolism JF bioRxiv FD Cold Spring Harbor Laboratory SP 043935 DO 10.1101/043935 A1 D. D. Scott A1 C. Trahan A1 P.J. Zindy A1 L.C. Aguilar A1 M.Y. Delubac A1 K. E. Wei A1 M. Oeffinger YR 2016 UL http://biorxiv.org/content/early/2016/03/16/043935.abstract AB Endo‐ and exonucleases are major contributors to RNA metabolism through their diverse roles in maturation and turnover of different species of RNA as well as transcription. Recent data suggests RNA nucleases also affect genome stability programs and act along DNA repair pathways. Here, we describe Nol12 as a multifunctional RNA/DNA endonuclease found in different subcellular compartments - the nucleoplasm, where it co-localizes with the RNA/DNA helicase Dhx9 and paraspeckles, nucleoli as well as GW/P-bodies. We show that Nol12 is required for a key step in ribosomal RNA processing, separating large and small subunit precursors at site 2, rerouting ribosome biogenesis via an alternative pathway in its absence to ensure ribosome production. Furthermore, loss of Nol12 results in increased oxidized DNA levels followed by a rapid p53-independent ATR-Chk1-mediated apoptotic response, suggesting a role for Nol12 in the prevention or resolution of oxidative DNA damage. Identification of a complex Nol12 interactome, which includes NONO, Dhx9 and DNA-PK, further supports its diverse functions in RNA metabolism and DNA maintenance, establishing Nol12 as a multifunctional endonuclease.