Previous Article | Next Article 
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.
This article has been cited by other articles:
-
Aygun, O., Xu, X., Liu, Y., Takahashi, H., Kong, S. E., Conaway, R. C., Conaway, J. W., Svejstrup, J. Q.
(2009). Direct Inhibition of RNA Polymerase II Transcription by RECQL5. J. Biol. Chem.
284: 23197-23203
[Abstract]
[Full Text]
-
Rosado, I. V., Niedzwiedz, W., Alpi, A. F., Patel, K. J.
(2009). The Walker B motif in avian FANCM is required to limit sister chromatid exchanges but is dispensable for DNA crosslink repair. Nucleic Acids Res
37: 4360-4370
[Abstract]
[Full Text]
-
Atkinson, J., McGlynn, P.
(2009). Replication fork reversal and the maintenance of genome stability. Nucleic Acids Res
37: 3475-3492
[Abstract]
[Full Text]
-
Zheng, L., Kanagaraj, R., Mihaljevic, B., Schwendener, S., Sartori, A. A., Gerrits, B., Shevelev, I., Janscak, P.
(2009). MRE11 complex links RECQ5 helicase to sites of DNA damage. Nucleic Acids Res
37: 2645-2657
[Abstract]
[Full Text]
-
Prakash, R., Satory, D., Dray, E., Papusha, A., Scheller, J., Kramer, W., Krejci, L., Klein, H., Haber, J. E., Sung, P., Ira, G.
(2009). Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination. Genes Dev.
23: 67-79
[Abstract]
[Full Text]
-
Hu, Y., Lu, X., Zhou, G., Barnes, E. L., Luo, G.
(2009). Recql5 Plays an Important Role in DNA Replication and Cell Survival after Camptothecin Treatment. Mol. Biol. Cell
20: 114-123
[Abstract]
[Full Text]
-
Liu, Y., West, S. C.
(2008). More complexity to the Bloom's syndrome complex. Genes Dev.
22: 2737-2742
[Abstract]
[Full Text]
-
Aygun, O., Svejstrup, J., Liu, Y.
(2008). A RECQ5-RNA polymerase II association identified by targeted proteomic analysis of human chromatin. Proc. Natl. Acad. Sci. USA
105: 8580-8584
[Abstract]
[Full Text]
-
Merkulov, S., Zhang, W.-M., Komar, A. A., Schmaier, A. H., Barnes, E., Zhou, Y., Lu, X., Iwaki, T., Castellino, F. J., Luo, G., McCrae, K. R.
(2008). Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis. Blood
111: 1274-1281
[Abstract]
[Full Text]
-
Brosh, R. M. Jr, Bohr, V. A.
(2007). Human premature aging, DNA repair and RecQ helicases. Nucleic Acids Res
35: 7527-7544
[Abstract]
[Full Text]
-
Branzei, D., Foiani, M.
(2007). RecQ helicases queuing with Srs2 to disrupt Rad51 filaments and suppress recombination. Genes Dev.
21: 3019-3026
[Full Text]
-
Hu, Y., Raynard, S., Sehorn, M. G., Lu, X., Bussen, W., Zheng, L., Stark, J. M., Barnes, E. L., Chi, P., Janscak, P., Jasin, M., Vogel, H., Sung, P., Luo, G.
(2007). RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev.
21: 3073-3084
[Abstract]
[Full Text]
-
Hartung, F., Suer, S., Puchta, H.
(2007). Two closely related RecQ helicases have antagonistic roles in homologous recombination and DNA repair in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA
104: 18836-18841
[Abstract]
[Full Text]
-
McVey, M., Andersen, S. L., Broze, Y., Sekelsky, J.
(2007). Multiple Functions of Drosophila BLM Helicase in Maintenance of Genome Stability. Genetics
176: 1979-1992
[Abstract]
[Full Text]
-
Xie, J., Bessling, S. L., Cooper, T. K., Dietz, H. C., McCallion, A. S., Fisher, S.
(2007). Manipulating Mitotic Recombination in the Zebrafish Embryo Through RecQ Helicases. Genetics
176: 1339-1342
[Abstract]
[Full Text]
-
Rockmill, B., Voelkel-Meiman, K., Roeder, G. S.
(2006). Centromere-Proximal Crossovers Are Associated With Precocious Separation of Sister Chromatids During Meiosis in Saccharomyces cerevisiae. Genetics
174: 1745-1754
[Abstract]
[Full Text]
-
Kanagaraj, R., Saydam, N., Garcia, P. L., Zheng, L., Janscak, P.
(2006). Human RECQ5{beta} helicase promotes strand exchange on synthetic DNA structures resembling a stalled replication fork. Nucleic Acids Res
0: gkl677v4-15
[Abstract]
[Full Text]
-
Ralf, C., Hickson, I. D., Wu, L.
(2006). The Bloom's Syndrome Helicase Can Promote the Regression of a Model Replication Fork. J. Biol. Chem.
281: 22839-22846
[Abstract]
[Full Text]
-
Seki, M., Nakagawa, T., Seki, T., Kato, G., Tada, S., Takahashi, Y., Yoshimura, A., Kobayashi, T., Aoki, A., Otsuki, M., Habermann, F. A., Tanabe, H., Ishii, Y., Enomoto, T.
(2006). Bloom Helicase and DNA Topoisomerase III{alpha} Are Involved in the Dissolution of Sister Chromatids.. Mol. Cell. Biol.
26: 6299-6307
[Abstract]
[Full Text]