title: RECQL, a member of the RecQ family of DNA helicases, suppresses chromosomal instability.
abstract: 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.
authors.affiliation: NIEHS MD A2-05, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Sharma
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Stumpo
authors.forename: Adayabalam S
authors.initials: AS
authors.lastname: Balajee
authors.forename: Cheryl B
authors.initials: CB
authors.lastname: Bock
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lansdorp
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brosh
authors.forename: Perry J
authors.initials: PJ
authors.lastname: Blackshear
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D043171:Chromosomal Instability / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D003703:Demecolcine / Q000494:pharmacology; D018274:Electroporation; D053595:Embryonic Stem Cells / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D017404:In Situ Hybridization, Fluorescence; D007211:Indoles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D011839:Radiation, Ionizing; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D012854:Sister Chromatid Exchange / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D005456:Fluorescent Dyes; D007211:Indoles; D012333:RNA, Messenger; C007293:DAPI; D053484:RecQ Helicases; D003703:Demecolcine