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Molecular and Cellular Biology, March 2007, p. 1784-1794, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01620-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

RECQL, a Member of the RecQ Family of DNA Helicases, Suppresses Chromosomal Instability{dagger} ,{triangledown}

Sudha Sharma,7,{ddagger} Deborah J. Stumpo,1,{ddagger} Adayabalam S. Balajee,6 Cheryl B. Bock,2 Peter M. Lansdorp,3 Robert M. Brosh Jr.,7* and Perry J. Blackshear1,4,5*

Laboratory of Neurobiology,1 Office of Clinical Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709,4 Duke Comprehensive Cancer Center,2 Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710,5 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada,3 Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, New York 10032,6 Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 212247

Received 30 August 2006/ Returned for modification 24 November 2006/ Accepted 5 December 2006

The mouse gene Recql is a member of the RecQ subfamily of DEx-H-containing DNA helicases. Five members of this family have been identified in both humans and mice, and mutations in three of these, BLM, WRN, and RECQL4, are associated with human diseases and a cellular phenotype that includes genomic instability. To date, no human disease has been associated with mutations in RECQL and no cellular phenotype has been associated with its deficiency. To gain insight into the physiological function of RECQL, we disrupted Recql in mice. RECQL-deficient mice did not exhibit any apparent phenotypic differences compared to wild-type mice. Cytogenetic analyses of embryonic fibroblasts from the RECQL-deficient mice revealed aneuploidy, spontaneous chromosomal breakage, and frequent translocation events. In addition, the RECQL-deficient cells were hypersensitive to ionizing radiation, exhibited an increased load of DNA damage, and displayed elevated spontaneous sister chromatid exchanges. These results provide evidence that RECQL has a unique cellular role in the DNA repair processes required for genomic integrity. Genetic background, functional redundancy, and perhaps other factors may protect the unstressed mouse from the types of abnormalities that might be expected from the severe chromosomal aberrations detected at the cellular level.

* Corresponding author. Mailing address for Perry J. Blackshear: NIEHS MD A2-05, 111 Alexander Drive, Research Triangle Park, NC 27709. Phone: (919) 541-4899. Fax: (919) 541-4571. E-mail: black009{at}niehs.nih.gov. Mailing address for Robert M. Brosh, Jr.: NIA, 5600 Nathan Shock Drive, Baltimore, MD 21224. Phone: (410) 558-8578. Fax: (410) 558-8157. E-mail: broshr{at}grc.nia.nih.gov.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{triangledown} Published ahead of print on 11 December 2006.

{ddagger} S.S. and D.J.S. contributed equally to this work.

Molecular and Cellular Biology, March 2007, p. 1784-1794, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01620-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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