Molecular and Cellular Biology, May 2005, p. 3431-3442, Vol. 25, No. 9
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.9.3431-3442.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Recql5 and Blm RecQ DNA Helicases Have Nonredundant Roles in Suppressing Crossovers
Yiduo Hu,1,2
Xincheng Lu,1,2
Ellen Barnes,1,2
Min Yan,1,3
Hua Lou,1,2 and
Guangbin Luo1,2*
Department of Genetics,1
Department of Molecular Biology and Microbiology, Case Western Reserve University,3
Case Comprehensive Cancer Center, University Hospitals of Cleveland, Cleveland, Ohio2
Received 30 November 2004/
Returned for modification 31 December 2004/
Accepted 2 February 2005
In eukaryotes, crossovers in mitotic cells can have deleterious consequences and therefore must be suppressed. Mutations in BLM give rise to Bloom syndrome, a disease that is characterized by an elevated rate of crossovers and increased cancer susceptibility. However, simple eukaryotes such as Saccharomyces cerevisiae have multiple pathways for suppressing crossovers, suggesting that mammals also have multiple pathways for controlling crossovers in their mitotic cells. We show here that in mouse embryonic stem (ES) cells, mutations in either the Bloom syndrome homologue (Blm) or the Recql5 genes result in a significant increase in the frequency of sister chromatid exchange (SCE), whereas deleting both Blm and Recql5 lead to an even higher frequency of SCE. These data indicate that Blm and Recql5 have nonredundant roles in suppressing crossovers in mouse ES cells. Furthermore, we show that mouse embryonic fibroblasts derived from Recql5 knockout mice also exhibit a significantly increased frequency of SCE compared with the corresponding wild-type control. Thus, this study identifies a previously unknown Recql5-dependent, Blm-independent pathway for suppressing crossovers during mitosis in mice.
* Corresponding author. Mailing address: Department of Genetics, Case Western Reserve University, BRB, 7th floor, 10900 Euclid Ave., Cleveland, OH 44106. Phone: (216) 844-7050. Fax: (216) 368-3432. E-mail: GXL35{at}case.edu.
Molecular and Cellular Biology, May 2005, p. 3431-3442, Vol. 25, No. 9
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.9.3431-3442.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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Copyright © 2005 by the American Society for Microbiology. All rights reserved.