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SAGA‐mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system
Author(s) -
Weake Vikki M,
Lee Kenneth K,
Guelman Sebastián,
Lin ChiaHui,
Seidel Christopher,
Abmayr Susan M,
Workman Jerry L
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601966
Subject(s) - biology , nonstop , genetics , mushroom bodies , microbiology and biotechnology , axon guidance , mutant , axon , drosophila melanogaster , gene , computer science , operating system
Nonstop, which has previously been shown to have homology to ubiquitin proteases, is required for proper termination of axons R1–R6 in the optic lobe of the developing Drosophila eye. Herein, we establish that Nonstop actually functions as an ubiquitin protease to control the levels of ubiquitinated histone H2B in flies. We further establish that Nonstop is the functional homolog of yeast Ubp8, and can substitute for Ubp8 function in yeast cells. In yeast, Ubp8 activity requires Sgf11. We show that in Drosophila , loss of Sgf11 function causes similar photoreceptor axon‐targeting defects as loss of Nonstop. Ubp8 and Sgf11 are components of the yeast SAGA complex, suggesting that Nonstop function might be mediated through the Drosophila SAGA complex. Indeed, we find that Nonstop does associate with SAGA components in flies, and mutants in other SAGA subunits display nonstop phenotypes, indicating that SAGA complex is required for accurate axon guidance in the optic lobe. Candidate genes regulated by SAGA that may be required for correct axon targeting were identified by microarray analysis of gene expression in SAGA mutants.