Originally published as Genetics Published Articles Ahead of Print on May 16, 2007.

Genetics, Vol. 176, 1979-1992, August 2007, Copyright © 2007
doi:10.1534/genetics.106.070052

Multiple Functions of Drosophila BLM Helicase in Maintenance of Genome Stability

Mitch McVey*,{dagger},{ddagger}, Sabrina L. Andersen§, Yuri Broze* and Jeff Sekelsky*,§,**,1

* Department of Biology, {dagger} SPIRE Program, § Curriculum in Genetics and Molecular Biology, ** Program in Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599 {ddagger} Department of Biology, Tufts University, Medford, Massachusetts 02155

1 Corresponding author: Department of Biology, CB 3280, 303 Fordham Hall, University of North Carolina, Chapel Hill, NC 27599-3280.
E-mail: sekelsky{at}unc.edu

Bloom Syndrome, a rare human disorder characterized by genomic instability and predisposition to cancer, is caused by mutation of BLM, which encodes a RecQ-family DNA helicase. The Drosophila melanogaster ortholog of BLM, DmBlm, is encoded by mus309. Mutations in mus309 cause hypersensitivity to DNA-damaging agents, female sterility, and defects in repairing double-strand breaks (DSBs). To better understand these phenotypes, we isolated novel mus309 alleles. Mutations that delete the N terminus of DmBlm, but not the helicase domain, have DSB repair defects as severe as those caused by null mutations. We found that female sterility is due to a requirement for DmBlm in early embryonic cell cycles; embryos lacking maternally derived DmBlm have anaphase bridges and other mitotic defects. These defects were less severe for the N-terminal deletion alleles, so we used one of these mutations to assay meiotic recombination. Crossovers were decreased to about half the normal rate, and the remaining crossovers were evenly distributed along the chromosome. We also found that spontaneous mitotic crossovers are increased by several orders of magnitude in mus309 mutants. These results demonstrate that DmBlm functions in multiple cellular contexts to promote genome stability.




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