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Molecular Cancer
Published in: Molecular Cancer 1/2011

Open Access 01-12-2011 | Research

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

Authors: Yumay Chen, Chi-Fen Chen, Huai-Chin Chiang, Michelle Pena, Rosaria Polci, Randy L Wei, Robert A Edwards, Donna E Hansel, Phang-Lang Chen, Daniel J Riley

Published in: Molecular Cancer | Issue 1/2011

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Abstract

Background

NEK1, 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.

Results

We 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.

Conclusion

NEK1 is required for the maintenance of genome stability by acting at multiple junctures, including control of chromosome stability.
Appendix
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Metadata
Title
Mutation of NIMA-related kinase 1 (NEK1) leads to chromosome instability
Authors
Yumay Chen
Chi-Fen Chen
Huai-Chin Chiang
Michelle Pena
Rosaria Polci
Randy L Wei
Robert A Edwards
Donna E Hansel
Phang-Lang Chen
Daniel J Riley
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2011
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-10-5

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