Originally published as Genetics Published Articles Ahead of Print on August 3, 2006.
Genetics, Vol. 174, 1273-1285, November 2006, Copyright © 2006
doi:10.1534/genetics.106.058289
Drosophila mus301/spindle-C Encodes a Helicase With an Essential Role in Double-Strand DNA Break Repair and Meiotic Progression
Ruth McCaffrey*,
,1,
Daniel St Johnston
and
Acaimo González-Reyes*,2
* MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom and
The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QR, United Kingdom
2 Corresponding author: Centro Andaluz de Biología del Desarrollo CSIC-UPO, Universidad Pablo de Olavide, Carretera de Utrera km 1, 41013 Sevilla, Spain.
E-mail: agonrey{at}upo.es
mus301 was identified independently in two genetic screens, one for mutants hypersensitive to chemical mutagens and another for maternal mutants with eggshell defects. mus301 is required for the proper specification of the oocyte and for progression through meiosis in the Drosophila ovary. We have cloned mus301 and show that it is a member of the Mus308 subfamily of ATP-dependent helicases and the closest homolog of human and mouse HEL308. Functional analyses demonstrate that Mus301 is involved in chromosome segregation in meiosis and in the repair of double-strand-DNA breaks in both meiotic and mitotic cells. Most of the oogenesis defects of mus301 mutants are suppressed by mutants in the checkpoint kinase Mei41 and in MeiW68, the Spo11 homolog that is thought to generate the dsDNA breaks that initiate recombination, indicating that these phenotypes are caused by activation of the DNA damage checkpoint in response to unrepaired Mei-W68-induced dsDNA breaks. However, neither mei-W68 nor mei-41 rescue the defects in oocyte specification of mus301 mutants, suggesting that this helicase has another function in oocyte selection that is independent from its role in meiotic recombination.
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J. D. Richards, K. A. Johnson, H. Liu, A.-M. McRobbie, S. McMahon, M. Oke, L. Carter, J. H. Naismith, and M. F. White
Structure of the DNA Repair Helicase Hel308 Reveals DNA Binding and Autoinhibitory Domains
J. Biol. Chem.,
February 22, 2008;
283(8):
5118 - 5126.
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Copyright © 2006 by the Genetics Society of America.