Sources and structures of mitotic crossovers that arise when BLM helicase is absent in Drosophila
The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions that block replication forks increased crossove...
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Published in | Genetics (Austin) Vol. 196; no. 1; pp. 107 - 118 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Genetics Society of America
01.01.2014
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Subjects | |
Online Access | Get full text |
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Summary: | The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions that block replication forks increased crossover frequencies, consistent with functions for BLM in responding to fork blockage. In contrast, treatment with hydroxyurea, which stalls forks, did not elevate crossovers, even though mutants lacking BLM are sensitive to killing by this agent. To learn about sources of spontaneous recombination, we mapped mitotic crossovers in mutants lacking BLM. In the male germline, irradiation-induced crossovers were distributed randomly across the euchromatin, but spontaneous crossovers were nonrandom. We suggest that regions of the genome with a high frequency of mitotic crossovers may be analogous to common fragile sites in the human genome. Interestingly, in the male germline there is a paucity of crossovers in the interval that spans the pericentric heterochromatin, but in the female germline this interval is more prone to crossing over. Finally, our system allowed us to recover pairs of reciprocal crossover chromosomes. Sequencing of these revealed the existence of gene conversion tracts and did not provide any evidence for mutations associated with crossovers. These findings provide important new insights into sources and structures of mitotic crossovers and functions of BLM helicase. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. Present address: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-8004. Present address: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27708. Present address: Department of Otolaryngology, University of North Carolina, Chapel Hill, NC 27599. Present address: Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695. Supporting information is available online at http://www.genetics.org/lookup/suppl/doi:10.1534/genetics.113.158618/-/DC1. |
ISSN: | 1943-2631 0016-6731 1943-2631 |
DOI: | 10.1534/genetics.113.158618 |