Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability

Molecular Cancer

Research

Donna E Hansel¹  Chi-Fen Chen²  Randy L Wei²  Phang-Lang Chen²  Yumay Chen³  Michelle Pena⁴  Huai-Chin Chiang⁴  Rosaria Polci⁵  Daniel J Riley⁶  Robert A Edwards⁷ 

[1] Department of Anatomic Pathology, Cleveland Clinic, 9500 Euclid Ave., 44195, Cleveland, OH, USA;Department of Biological Chemistry, University of California at Irvine, Medical Science 1, 92697, Irvine, CA, USA;Department of Medicine, Division of Endocrinology, University of California at Irvine, 1130 Gross Hall, 92697, Irvine, CA, USA;Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78229, San Antonio, TX, USA;Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78229, San Antonio, TX, USA;Department of Nephrology and Dialysis, Belcolle Hospital, Viterbo, Italy;Department of Medicine, Division of Nephrology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78229, San Antonio, TX, USA;Transplant Center, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78229, San Antonio, TX, USA;Department of Pathology and Lab Medicine, University of California at Irvine, Medical Science 1, 92697, Irvine, CA, USA;

关键词: Wild Type Cell;    Mitotic Spindle;    Primary Cilium;    Ataxia Telangiectasia Mutate;    Wild Type Littermate;   

DOI  :  10.1186/1476-4598-10-5

 received in 2010-04-13, accepted in 2011-01-10,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundNEK1, the first mammalian ortholog of the fungal protein kinase never-in-mitosis A (NIMA), is involved early in the DNA damage sensing/repair pathway. A defect in DNA repair in NEK1-deficient cells is suggested by persistence of DNA double strand breaks after low dose ionizing radiation (IR). NEK1-deficient cells also fail to activate the checkpoint kinases CHK1 and CHK2, and fail to arrest properly at G1/S or G2/M-phase checkpoints after DNA damage.ResultsWe show here that NEK1-deficient cells suffer major errors in mitotic chromosome segregation and cytokinesis, and become aneuploid. These NEK1-deficient cells transform, acquire the ability to grow in anchorage-independent conditions, and form tumors when injected into syngeneic mice. Genomic instability is also manifest in NEK1 +/- mice, which late in life develop lymphomas with a much higher incidence than wild type littermates.ConclusionNEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.

【 授权许可】

CC BY   
© Chen et al; licensee BioMed Central Ltd. 2011